NO136649B - - Google Patents
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- NO136649B NO136649B NO2109/71A NO210971A NO136649B NO 136649 B NO136649 B NO 136649B NO 2109/71 A NO2109/71 A NO 2109/71A NO 210971 A NO210971 A NO 210971A NO 136649 B NO136649 B NO 136649B
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- Norway
- Prior art keywords
- testosterone
- cyclopentylpropionate
- hydroxy
- nortestosterone
- epoxy
- Prior art date
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
- KHKDIUPVDIEHAH-UHFFFAOYSA-N (4-hydroxy-13-methyl-3-oxo-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-17-yl) 3-cyclopentylpropanoate Chemical compound CC12CCC(C3CCC(=O)C(O)=C3CC3)C3C1CCC2OC(=O)CCC1CCCC1 KHKDIUPVDIEHAH-UHFFFAOYSA-N 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 9
- 230000001195 anabolic effect Effects 0.000 claims description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- 229960004719 nandrolone Drugs 0.000 claims description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- NPAGDVCDWIYMMC-IZPLOLCNSA-N nandrolone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 NPAGDVCDWIYMMC-IZPLOLCNSA-N 0.000 claims description 4
- PFSLCDNYNJTYDO-UHFFFAOYSA-N 2-cyclopentylpropanoyl chloride Chemical compound ClC(=O)C(C)C1CCCC1 PFSLCDNYNJTYDO-UHFFFAOYSA-N 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 150000003512 tertiary amines Chemical class 0.000 claims description 3
- 230000002045 lasting effect Effects 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- -1 compound 4-hydroxy-19-nortestosterone-17-cyclopentylpropionate Chemical class 0.000 description 4
- 210000003205 muscle Anatomy 0.000 description 4
- 230000001016 myotrophic effect Effects 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 229960000921 testosterone cypionate Drugs 0.000 description 3
- HPFVBGJFAYZEBE-ZLQWOROUSA-N testosterone cypionate Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(CCC(=O)C=C4CC3)C)CC[C@@]21C)C(=O)CCC1CCCC1 HPFVBGJFAYZEBE-ZLQWOROUSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- 230000001548 androgenic effect Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000005923 long-lasting effect Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 231100001274 therapeutic index Toxicity 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- REWKEGSQGOSEES-FNKXXKKYSA-N 17beta-Hydroxyestr-4-en-3-one cyclopentanepropionate Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@H]4CCC(=O)C=C4CC3)CC[C@@]21C)C(=O)CCC1CCCC1 REWKEGSQGOSEES-FNKXXKKYSA-N 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- 206010041277 Sodium retention Diseases 0.000 description 1
- 208000010399 Wasting Syndrome Diseases 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- GXHBCWCMYVTJOW-YGRHGMIBSA-N oxabolone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1O GXHBCWCMYVTJOW-YGRHGMIBSA-N 0.000 description 1
- 229950010171 oxabolone Drugs 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 231100000161 signs of toxicity Toxicity 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
Classifications
-
- E—FIXED CONSTRUCTIONS
- E02—HYDRAULIC ENGINEERING; FOUNDATIONS; SOIL SHIFTING
- E02B—HYDRAULIC ENGINEERING
- E02B17/00—Artificial islands mounted on piles or like supports, e.g. platforms on raisable legs or offshore constructions; Construction methods therefor
- E02B17/02—Artificial islands mounted on piles or like supports, e.g. platforms on raisable legs or offshore constructions; Construction methods therefor placed by lowering the supporting construction to the bottom, e.g. with subsequent fixing thereto
- E02B17/027—Artificial islands mounted on piles or like supports, e.g. platforms on raisable legs or offshore constructions; Construction methods therefor placed by lowering the supporting construction to the bottom, e.g. with subsequent fixing thereto steel structures
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B63—SHIPS OR OTHER WATERBORNE VESSELS; RELATED EQUIPMENT
- B63B—SHIPS OR OTHER WATERBORNE VESSELS; EQUIPMENT FOR SHIPPING
- B63B35/00—Vessels or similar floating structures specially adapted for specific purposes and not otherwise provided for
- B63B35/08—Ice-breakers or other vessels or floating structures for operation in ice-infested waters; Ice-breakers, or other vessels or floating structures having equipment specially adapted therefor
- B63B35/12—Ice-breakers or other vessels or floating structures for operation in ice-infested waters; Ice-breakers, or other vessels or floating structures having equipment specially adapted therefor having ice-cutters
-
- E—FIXED CONSTRUCTIONS
- E02—HYDRAULIC ENGINEERING; FOUNDATIONS; SOIL SHIFTING
- E02B—HYDRAULIC ENGINEERING
- E02B17/00—Artificial islands mounted on piles or like supports, e.g. platforms on raisable legs or offshore constructions; Construction methods therefor
- E02B17/0017—Means for protecting offshore constructions
- E02B17/0021—Means for protecting offshore constructions against ice-loads
-
- E—FIXED CONSTRUCTIONS
- E02—HYDRAULIC ENGINEERING; FOUNDATIONS; SOIL SHIFTING
- E02B—HYDRAULIC ENGINEERING
- E02B17/00—Artificial islands mounted on piles or like supports, e.g. platforms on raisable legs or offshore constructions; Construction methods therefor
- E02B2017/0056—Platforms with supporting legs
- E02B2017/0073—Details of sea bottom engaging footing
- E02B2017/0086—Large footings connecting several legs or serving as a reservoir for the storage of oil or gas
Landscapes
- Engineering & Computer Science (AREA)
- General Engineering & Computer Science (AREA)
- Mechanical Engineering (AREA)
- Civil Engineering (AREA)
- Structural Engineering (AREA)
- Chemical & Material Sciences (AREA)
- Combustion & Propulsion (AREA)
- Ocean & Marine Engineering (AREA)
- Earth Drilling (AREA)
- Disintegrating Or Milling (AREA)
- Steroid Compounds (AREA)
Description
Fremgangsmåte til fremstilling av 4-hydroksy-19-nortestosteron-17- cyclopentylpropionat. Process for the production of 4-hydroxy-19-nortestosterone-17-cyclopentylpropionate.
Foreliggende oppfinnelse angår en fremgangsmåte til fremstilling av 4-hydroxy-19-nortestosteron-17-cyclo-pentylpropionat med følgende strukturformel: The present invention relates to a method for the production of 4-hydroxy-19-nortestosterone-17-cyclopentylpropionate with the following structural formula:
Denne forbindelse er meget verdifull This connection is very valuable
grunn av dens styrke og dens lang-varige myotrofiske virkning. due to its strength and its long-lasting myotrophic effect.
Visse estre av 4-hy dr oxy-19-nor testo-steron og også noen analoge forbindelser, Certain esters of 4-hydroxy-19-nor testosterone and also some analogous compounds,
f. eks. testosteroncyclopentyl-propionat og e.g. testosterone cyclopentyl-propionate and
19-nortestosteroncyclopentylpropionat har 19-nortestosterone cyclopentylpropionate has
den samme generelle virkning, men ingen the same general effect, but none
av forbindelsene utøver, såvidt vites, en of the compounds exercise, as far as is known, one
så høy og-en så langvarig virkning som den as high and as long-lasting an effect as that
forbindelse som fremstilles ifølge oppfinnelsen. compound produced according to the invention.
Den nye forbindelse 4-hydroxy-19-nortestosteron-17-cyclopentylpropionat har The new compound 4-hydroxy-19-nortestosterone-17-cyclopentylpropionate has
i form av oppløsninger i. flytende bærere, in the form of solutions in. liquid carriers,
f. eks., vegetabilske oljer, et glycol, en gel eg, vegetable oils, a glycol, a gel
eller;i form av en mikrokrystallinsk'.suspensjon i vandige media, en utpreget akutt or; in the form of a microcrystalline suspension in aqueous media, a distinctly acute
såvel som' en forlenget myotrofisk virkning. as well as' a prolonged myotrophic effect.
Disse karakteristika gjør forbindelsen og These characteristics make the connection and
blandinger som inneholder den, verdifulle ved behandlingen av visse patologiske til-stander, f. eks. slike som skyldes protein-tap. Den myotrofiske virkning av produk-tet av fremgangsmåten ifølge den foreliggende oppfinnelse er høyere enn for testo-steroncyclopentylpropionat fra den 7de til den 28de dag. Omvendt er den androgene virkning meget svakere. Den terapeutiske indeks for den nye forbindelse er derfor bestemt mere fordelaktig enn for testo-steroncyclopentylpropionat. 4-hydroxy-19-nortestosteron-17-cyclopentylpropionat er også anvendt av mennesker i doser på 50 mg engang i uken. De oppnådde resultater viser at den nye forbindelse har en god anabolisk effekt (nitrogen retensjon, øking av kroppsvekt, velbefinnende, bedring av svinnsykdommer etc.) uten tilsynelatende androgene egenskaper. Det var ingen tyde- mixtures containing it, valuable in the treatment of certain pathological conditions, e.g. such as those due to protein loss. The myotrophic effect of the product of the method according to the present invention is higher than that of testosterone cyclopentyl propionate from the 7th to the 28th day. Conversely, the androgenic effect is much weaker. The therapeutic index of the new compound is therefore decidedly more favorable than that of testosterone cyclopentyl propionate. 4-hydroxy-19-nortestosterone-17-cyclopentylpropionate has also been used by humans in doses of 50 mg once a week. The results obtained show that the new compound has a good anabolic effect (nitrogen retention, increase in body weight, well-being, improvement of wasting diseases, etc.) without apparent androgenic properties. There was no clue-
lige tegn på giftvirkning. I særdeleshet steg ikke blodtrykket, heller ikke opptrådte der noen natriumretensjon. Lignende fordel-aktige resultater er iakttatt hos for tidlig modne barn og hos hemmede barn eller ved vekstmangler som er behandlet ved innsprøytning av doser som er lavere enn 0,5 mg/kg en gang pr. uke. even signs of toxicity. In particular, the blood pressure did not rise, nor did any sodium retention occur. Similar beneficial results have been observed in precocious children and in stunted children or in growth deficiencies treated by injection of doses lower than 0.5 mg/kg once a day. week.
Ved hjelp av oppfinnelsen skaffes der således en fremgangsmåte til fremstilling av 4-hydroxy-19-nortestosteron- 17-cyclo-pentylpropionat med den ovenstående strukturformel. Det karakteristiske hoved-trekk ved denne fremgangsmåte er at 19-nor-testosteronet, oppløst i et organisk opp-løsningsmiddel, på kjent måte epoxyderes med hydrogenperoxyd i et alkalisk medium, og at det resulterende 4,5-epoxy-19-nor-testosteron omsettes med cyclopentyl-propionsyreklorid i nærvær av et tertiært amin, hvorefter det således erholdte 4,5-epoxy- 19-nor-testosteron-17-cyclopentyl-propionat omsettes med svovelsyre i nærvær av eddiksyre. With the help of the invention, a method for the production of 4-hydroxy-19-nortestosterone-17-cyclo-pentylpropionate with the above structural formula is thus obtained. The characteristic main feature of this method is that the 19-nor-testosterone, dissolved in an organic solvent, is epoxidized in a known manner with hydrogen peroxide in an alkaline medium, and that the resulting 4,5-epoxy-19-nor-testosterone is reacted with cyclopentyl propionic acid chloride in the presence of a tertiary amine, after which the thus obtained 4,5-epoxy-19-nor-testosterone-17-cyclopentyl-propionate is reacted with sulfuric acid in the presence of acetic acid.
Det organiske oppløsningsmiddel er fortrinsvis et med vann blandbart oppløs-ningsmiddel, f. eks. methanol eller ethanol. The organic solvent is preferably a water-miscible solvent, e.g. methanol or ethanol.
Som eksempler på det tertiære amin som anvendes kan nevnes pyridin og di-methylanilin. Examples of the tertiary amine used are pyridine and dimethylaniline.
Behandlingen med svovelsyre av mel-lomproduktet 4,5-epoxy-19-nor-testoster-on-17-cyclopentylpropionatet, som utskil-les fra reaksjonsblandingen, utføres ved omtrent værelsestemperatur. The treatment with sulfuric acid of the intermediate product 4,5-epoxy-19-nor-testosterone-one-17-cyclopentylpropionate, which is separated from the reaction mixture, is carried out at approximately room temperature.
Trinnene i fremgangsmåten ifølge oppfinnelsen illustreres ved følgende reak-sjonsskjema: The steps in the method according to the invention are illustrated by the following reaction scheme:
Oppfinnelsen illustreres av følgende eksempler: Eksempel I. 4, 5- epoxy- 19- nortestosteron- 17- cyclo-pentylpropionat. The invention is illustrated by the following examples: Example I. 4, 5-epoxy-19-nortestosterone-17-cyclopentylpropionate.
20,4 ml vandig 4 N NaOH og 96 ml 35 pst. H202 blir samtidig tilsatt til en oppløs- 20.4 ml of aqueous 4 N NaOH and 96 ml of 35% H202 are simultaneously added to a solvent
ning av 40 g av 19-nortestosteron oppløst i 800 ml methanol ved 15° C. Oppløsningen blir tillatt å stå ved omtrent 0° C i 30 minutter og deretter blir den ansyret med 6 ml eddiksyre. Blandingen blir deretter ning of 40 g of 19-nortestosterone dissolved in 800 ml of methanol at 15° C. The solution is allowed to stand at about 0° C for 30 minutes and then it is acidified with 6 ml of acetic acid. The mixture then becomes
fortynnet med en vandig oppløsning av NaCl og ekstrahert med ethylacetat. Eks-traktet blir vasket til nøytral reaksjon og diluted with an aqueous solution of NaCl and extracted with ethyl acetate. The extract is washed to a neutral reaction and
deretter inndampet og det oljeaktige resi-duum (som består av 4a,5a-epoxy og 4|3,5|3-epoxy-19-nortestosteron) blir oppløst i 150 ml pyridin. Oppløsningen blir avkjølt til — 10° C og behandlet under omrøring og over en periode på 1 time med 40 ml cyclo-pentylpropionsyreklorid. Etter henstand natten over ved 0° C blir isvann tilsatt og det utfelte stoff filtrert fra og vasket med vann. Det ble oppnådd 72 g av et urent produkt som ble krystallisert fra en blanding av ether og petrolether. then evaporated and the oily residue (consisting of 4α,5α-epoxy and 4|3,5|3-epoxy-19-nortestosterone) is dissolved in 150 ml of pyridine. The solution is cooled to -10° C. and treated with stirring over a period of 1 hour with 40 ml of cyclopentylpropionic acid chloride. After standing overnight at 0° C, ice water is added and the precipitated substance is filtered off and washed with water. 72 g of an impure product was obtained which was crystallized from a mixture of ether and petroleum ether.
Utbytte: 45,5 g av en blanding av 4a,5a-epoxy- og 4(3,5(3-epoxy-19-nortestosteron-17-cyclopentylpropionat. Yield: 45.5 g of a mixture of 4a,5a-epoxy- and 4(3,5(3-epoxy-19-nortestosterone-17-cyclopentylpropionate.
Eksempel II. Example II.
4- hydroxy- 19- nortestosteron- 17- cyclopen-tylpropionat. 4- hydroxy- 19- nortestosterone- 17- cyclopentyl propionate.
En suspensjon av 45,5 mg av det fore-gående produkt i 14,4 ml eddiksyre blir behandlet med en blanding av 54 ml éddik-syre og 13,5 ml kons. H2SO(. En fullstendig oppløsning resulterte og etter 10 minutter utfelles et fast produkt. Etter henstand i 1 time ved værelsestemperatur blir produk-tet filtrert, vasket med eddiksyre, deretter med vann og tilslutt tørket under vakuum. A suspension of 45.5 mg of the preceding product in 14.4 ml of acetic acid is treated with a mixture of 54 ml of acetic acid and 13.5 ml of conc. H2SO(. A complete dissolution resulted and after 10 minutes a solid product precipitates. After resting for 1 hour at room temperature, the product is filtered, washed with acetic acid, then with water and finally dried under vacuum.
Det blir oppnådd 24 g av 4-hydroxy-19-nortestosteron-cyclopentylpropionat, 24 g of 4-hydroxy-19-nortestosterone-cyclopentylpropionate are obtained,
smp. 158—160° C, X maks. = 276 m^i, e m.p. 158—160° C, X max. = 276 m^i, e
13.050. Fra moderlutene er det mulig å gjenvinne ved ekstraksjon med methylen-klorid ytterligere 3 g av det samme produkt som smelter ved 155—157° C. 13,050. From the mother liquors, it is possible to recover by extraction with methylene chloride a further 3 g of the same product which melts at 155-157°C.
[a]D = + 38° (c = 1 pet. i CHC1S). [a]D = + 38° (c = 1 pet. in CHC1S).
Eksempel III. Example III.
Farmakologisk effekt av 4- hydroxy- 19-nortestosteron- 17- cyclopentylpropionat. Pharmacological effect of 4-hydroxy-19-nortestosterone-17-cyclopentylpropionate.
4-hydroxy-19-nortestosteron-cyclopen-tylpropionat ble prøvet på kastrerte han-rotter med en kroppsvekt på 50 g ved sub-kutan innsprøytning av en enkelt dose av steroidet oppløst i olivenolje. Dyrene ble drept 7, 14, 21 og 28 dager etter innsprøyt-ningen og vekten av levator ani-muskel og ventral prostata ble notert. Resultatene er angitt i tabell I. 4-hydroxy-19-nortestosterone-cyclopentylpropionate was tested on castrated male rats with a body weight of 50 g by subcutaneous injection of a single dose of the steroid dissolved in olive oil. The animals were killed 7, 14, 21 and 28 days after the injection and the weight of the levator ani muscle and ventral prostate was noted. The results are shown in Table I.
Tabell I. Table I.
Forlenget virkning av 4- hydroxy- 19-nortestosteron- 17- cyclopentylpropionat. Prolonged action of 4-hydroxy-19-nortestosterone-17-cyclopentylpropionate.
Dosen blir uttrykt som mg av testo-steron og organets vekt i mg/100 g av kroppsvekt. Terapeutisk indeks (T. I.) blir definert ved forholdet i vektøkningen av levator ani-muskel (lev.ani) og ventral prostata (V.Prost.) idet begge refererer til kontrolldyr. The dose is expressed as mg of testosterone and the weight of the organ in mg/100 g of body weight. Therapeutic index (T.I.) is defined by the ratio in the weight gain of levator ani muscle (lev.ani) and ventral prostate (V.Prost.), as both refer to control animals.
Den .varige anaboliske virkning av 4-hydroxy-19-nor-testosteron-17-cyclopen-tylpropionat er 2,5 ganger høyere, enn for 4-hydroxy-testosteron-17-cyclopentylpro-pionat og meget høyere enn for testosteron-17-cyclopentylpropionat. The lasting anabolic effect of 4-hydroxy-19-nor-testosterone-17-cyclopentylpropionate is 2.5 times higher than that of 4-hydroxy-testosterone-17-cyclopentylpropionate and much higher than that of testosterone-17- cyclopentyl propionate.
I sammenligningsøyemed ble 4-hydroxy-19-nor-testoster.on-17-cyclopentyl-propionat, 4-hydroxy-testosteron-17-cyclo-pentylpropionat og 19-nor-testosteron-17-cyclopentylpropionat prøvet på anabolisk virkning etter den metode som er beskrevet av Hershberger et al. (Proe. Soc. Exp. Biol. and Med. 83. 1953 s. 175) i henhold til føl-gende fremgangsmåte: Det ble anvendt grupper på syv eller flere, på forhånd kastrerte albinorotter som veide fra 30 til 40 g. Steroidene ble tilberedt i olje og inngitt subkutant. Etter behandlingen ble dyrene obdusert.'Levator ani-muskelen ble fjernet, og våtvekten notert. I forutgående forsøk ble også tørrvektene notert, men da der ikke ble funnet noen tegn til hydratisering, ble våtv.ektene.anvendt gjennom hele eks-perimentet. Myotrofisk (dvs. anabolisk) aktivitet ble bestemt ved økningen av vekten av levator ani-muskelen. For comparison purposes, 4-hydroxy-19-nor-testosterone-17-cyclopentyl-propionate, 4-hydroxy-testosterone-17-cyclopentylpropionate and 19-nor-testosterone-17-cyclopentylpropionate were tested for anabolic effects according to the method is described by Hershberger et al. (Proe. Soc. Exp. Biol. and Med. 83. 1953 p. 175) according to the following procedure: Groups of seven or more previously castrated albino rats weighing from 30 to 40 g were used. The steroids were prepared in oil and administered subcutaneously. After treatment, the animals were necropsied. The levator ani muscle was removed and the wet weight noted. In previous experiments, the dry weights were also noted, but as no signs of hydration were found, the wet weights were used throughout the experiment. Myotrophic (ie, anabolic) activity was determined by the increase in the weight of the levator ani muscle.
Resultatene med henblikk på akutt anabolisk virkning er oppført i Tabell II (daglig behandling i 7 dager). The results with regard to acute anabolic effect are listed in Table II (daily treatment for 7 days).
De resultater som er angitt i tabell II viser at 4-hydroxy-19-nor-testosteron-17-cyclopentylpropionatet bevirker en akutt anabolisk virkning som er minst 10 ganger større enn for 4-hydroxy-testosteron-17-cyclopentylpropionat og minst to ganger større enn for 19-nor-testosteron-17-cyclo-pentylpropionat. The results shown in Table II show that the 4-hydroxy-19-nor-testosterone-17-cyclopentylpropionate causes an acute anabolic effect which is at least 10 times greater than that of 4-hydroxy-testosterone-17-cyclopentylpropionate and at least two times greater than for 19-nor-testosterone-17-cyclopentylpropionate.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO770363A NO770363L (en) | 1970-06-15 | 1977-02-03 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4627370A | 1970-06-15 | 1970-06-15 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO136649B true NO136649B (en) | 1977-07-04 |
| NO136649C NO136649C (en) | 1977-10-12 |
Family
ID=21942554
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO2109/71A NO136649C (en) | 1970-06-15 | 1971-06-04 | DEVICE FOR} PREVENTING ICE DAMAGE ON MARITIME CONSTRUCTIONS |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US3669052A (en) |
| JP (4) | JPS56168534U (en) |
| CA (2) | CA943779A (en) |
| DE (1) | DE2127471A1 (en) |
| GB (1) | GB1347572A (en) |
| NO (1) | NO136649C (en) |
| SE (1) | SE391549B (en) |
| SU (1) | SU936820A3 (en) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3868920A (en) * | 1970-09-23 | 1975-03-04 | Air Logistics Corp | Semi-submerged cargo transport system |
| US3759046A (en) * | 1972-03-23 | 1973-09-18 | Global Marine Inc | Movement of marine structures in saline ice |
| US3894504A (en) * | 1974-04-08 | 1975-07-15 | Sea Log Corp | Ice cutter for monopod drilling platform |
| US4063428A (en) * | 1975-08-26 | 1977-12-20 | Heinrich Waas | Method of deflecting ice at upright columns submerged in water of stationary or floating structures in marine areas in which the occurence of ice may be expected, and ice deflector assembly therefor |
| JPS5364901A (en) * | 1976-11-24 | 1978-06-09 | Mitsui Shipbuilding Eng | Ice crusher for structure used in icy waters |
| US4102288A (en) * | 1977-02-28 | 1978-07-25 | Sun Oil Company Limited | Operations vessel for ice covered seas |
| US4260292A (en) * | 1979-10-25 | 1981-04-07 | The Offshore Company | Arctic offshore platform |
| US4350114A (en) * | 1980-03-17 | 1982-09-21 | Sea-Log Corporation | Semi-submersible tanker with directional ice cutters |
| FI82112C (en) * | 1982-06-15 | 1991-01-10 | Masa Yards Oy | Protection procedure and device |
| JPH0739756Y2 (en) * | 1987-08-21 | 1995-09-13 | 石川島播磨重工業株式会社 | Floating structure |
| WO2010126629A1 (en) | 2009-04-30 | 2010-11-04 | Exxonmobil Upstream Research Company | Mooring system for floating arctic vessel |
| US20120128427A1 (en) * | 2010-10-21 | 2012-05-24 | Conocophillips Company | Leg ice shields for ice worthy jack-up drilling unit |
| US9181670B2 (en) * | 2013-05-17 | 2015-11-10 | National Research Council Of Canada | Large scale spallation inducing ice protection |
| RU164346U1 (en) * | 2014-08-11 | 2016-08-27 | Блю Кэпитал Пте. Лтд. | MARINE FACILITY FOR DRILLING, PRODUCING AND / OR STORAGE OF MARINE DEPOSIT PRODUCTS |
| RU171716U1 (en) * | 2017-02-14 | 2017-06-13 | Федеральное государственное автономное образовательное учреждение высшего образования "Дальневосточный федеральный университет" (ДВФУ) | Device for protecting offshore drilling rigs from ice |
| CN107469986B (en) * | 2017-08-09 | 2019-01-11 | 嘉兴凯蒂市场营销策划有限公司 | One kind is built for substation with intelligent stone breaking machine device people |
| US10683629B2 (en) * | 2018-10-10 | 2020-06-16 | Pro-Built Docks, LLC | Ice ramp system, bracket, and method |
| RU2746339C1 (en) * | 2020-07-02 | 2021-04-12 | Федеральное государственное бюджетное учреждение "3 Центральный научно-исследовательский институт" Министерства обороны Российской Федерации | Universal dismountable ice cutter |
-
1970
- 1970-06-15 US US46273A patent/US3669052A/en not_active Expired - Lifetime
-
1971
- 1971-06-03 DE DE19712127471 patent/DE2127471A1/en not_active Withdrawn
- 1971-06-04 NO NO2109/71A patent/NO136649C/en unknown
- 1971-06-11 GB GB2740571A patent/GB1347572A/en not_active Expired
- 1971-06-11 CA CA115,389A patent/CA943779A/en not_active Expired
- 1971-06-14 SU SU711675251A patent/SU936820A3/en active
- 1971-06-14 SE SE7107705A patent/SE391549B/en unknown
-
1974
- 1974-07-05 CA CA204,124A patent/CA968168B/en not_active Expired
-
1981
- 1981-05-01 JP JP1981062689U patent/JPS56168534U/ja active Pending
- 1981-05-01 JP JP1981062692U patent/JPS5738831U/ja active Pending
- 1981-05-01 JP JP1981062690U patent/JPS5746636U/ja active Pending
- 1981-05-01 JP JP1981062691U patent/JPS5746637U/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JPS56168534U (en) | 1981-12-12 |
| JPS5746637U (en) | 1982-03-15 |
| CA943779A (en) | 1974-03-19 |
| NO136649C (en) | 1977-10-12 |
| US3669052A (en) | 1972-06-13 |
| GB1347572A (en) | 1974-02-27 |
| CA968168B (en) | 1975-05-27 |
| DE2127471A1 (en) | 1971-12-23 |
| JPS5738831U (en) | 1982-03-02 |
| SE391549B (en) | 1977-02-21 |
| JPS5746636U (en) | 1982-03-15 |
| SU936820A3 (en) | 1982-06-15 |
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