CS248730B2 - Production method of 6alfa methylcorticoid derivatives - Google Patents
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- CS248730B2 CS248730B2 CS8410076A CS1007684A CS248730B2 CS 248730 B2 CS248730 B2 CS 248730B2 CS 8410076 A CS8410076 A CS 8410076A CS 1007684 A CS1007684 A CS 1007684A CS 248730 B2 CS248730 B2 CS 248730B2
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- methyl
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- methylcorticoid
- 6alfa
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- 238000004519 manufacturing process Methods 0.000 title description 3
- 238000000034 method Methods 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 239000003470 adrenal cortex hormone Substances 0.000 claims 1
- -1 isobutyryl Chemical group 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-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
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000005051 trimethylchlorosilane Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- VDNZZIYSCXESNI-VFDAWVHUSA-N (6S,8S,9S,10R,11R,13S,14S,17S)-17-acetyl-11-hydroxy-6,10,13-trimethyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-one Chemical compound O[C@H]1[C@@H]2[C@]3(C=CC(C=C3[C@H](C[C@H]2[C@@H]2CC[C@H](C(C)=O)[C@]2(C1)C)C)=O)C VDNZZIYSCXESNI-VFDAWVHUSA-N 0.000 description 1
- KOPMZTKUZCNGFY-UHFFFAOYSA-N 1,1,1-triethoxybutane Chemical compound CCCC(OCC)(OCC)OCC KOPMZTKUZCNGFY-UHFFFAOYSA-N 0.000 description 1
- FGWYWKIOMUZSQF-UHFFFAOYSA-N 1,1,1-triethoxypropane Chemical compound CCOC(CC)(OCC)OCC FGWYWKIOMUZSQF-UHFFFAOYSA-N 0.000 description 1
- ABUFEAKDTQPJQZ-UHFFFAOYSA-N 2,2-diethylbutane-1,1,1-triol Chemical compound CCC(CC)(CC)C(O)(O)O ABUFEAKDTQPJQZ-UHFFFAOYSA-N 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012455 Dermatitis exfoliative Diseases 0.000 description 1
- 206010028116 Mucosal inflammation Diseases 0.000 description 1
- 201000010927 Mucositis Diseases 0.000 description 1
- 241000269908 Platichthys flesus Species 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 208000028004 allergic respiratory disease Diseases 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002168 ethanoic acid esters Chemical class 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- BQFPCTXLBRVFJL-UHFFFAOYSA-N triethoxymethylbenzene Chemical compound CCOC(OCC)(OCC)C1=CC=CC=C1 BQFPCTXLBRVFJL-UHFFFAOYSA-N 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000003905 vulva Anatomy 0.000 description 1
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- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
(54) Způsob výroby derivátů Ba-methylkortikoidu(54) A method for producing B-methylcorticoid derivatives
Vynález se týká způsobu výroby nových derivátů 6#-methylkortikoidu obecného vzorce IThe invention relates to a process for the preparation of novel 6'-methylcorticoid derivatives of the formula I
CH3 (!) ve kterém CH 3 (!) In which
V-T— znamená jednoduchou nebo dvojnou vazbu,V-T— means a single or double bond,
R znamená acyloxyskupinu s nejvýše 8 atomy uhlíku, aR is acyloxy having no more than 8 carbon atoms, and
X‘ znamená atom chloru.X ‘represents a chlorine atom.
Nové 6a-methylkortikoidy obecného vzorce I mohou jako acyloxyskupiny ve významu symbolu R obsahovat alifatické, cykloalifatické nebo aromatické zbytky, jako jsou například acetylová skupina, propionylová skupina, butyrylová skupina, isobutyrylová skupina, valerylová skupina, 3-methylbutyrylová skupina, trimethylacetylová skupina, hexanoylová skupina nebo benzoylová skupina.The novel 6α-methyl corticoids of the formula I may contain as acyloxy groups in the meaning of R the aliphatic, cycloaliphatic or aromatic radicals such as acetyl, propionyl, butyryl, isobutyryl, valeryl, 3-methylbutyryl, trimethylacetyl, hexanoyl or a benzoyl group.
Bylo zjištěno, že nové 6a-methylkortikoidy obecného vzorce I, vyrobené způsobem podle vynálezu, mají při lokální aplikaci často silnější účinnost než až dosud známé 6«-methylkortikoidy. Tato účinnost je často dokonce ještě významněji silnější, než je účinnost dvojnásobně fluorovaných„ušlechtilých“ kortikoidů, jako je třeba 6a,9a-dífluor-ll13-hydroxy-16a-methyl-21-valeryloxy-l,4-pregnadien-3,20-díon (tj. Nerisona).It has been found that the novel 6α-methyl corticoids of the formula (I) produced by the process according to the invention often have a stronger activity when applied topically than the hitherto known 6'-methyl corticoids. This activity is often even significantly greater than the efficiency of doubly fluorinated "noble" glucocorticoids, such as 6a, 9a-difluoro-1 3-hydroxy-16-methyl-21-valeryloxy-l, 4-pregnadiene-3, 20-daon (ie Nerison).
Při systemické aplikaci jsou tyto 6a-methylkortikoidy překvapivě často slaběji účinné než příslušné dosud známé 6«-methylkortikoidy.Surprisingly, in systemic application, these 6α-methyl corticoids are often less potent than the corresponding 6-methyl corticoids known so far.
Nové 6a-methylkortikoidy obecného vzorce I, vyrobené způsobem podle vynálezu, jsou proto vhodné v kombinaci s nosiči obvyklými v galenické farmacii k lokálnímu ošetření kontaktní dermititidy, ekzémů nejrůznějšího druhu, neurodermatóz, erythrodermie, spálenin, svědění vulvy a řitě, trudoviny růžovité, kožního erythematodu, lupénky, lišeje plochého červeného a bradavčitého a podobných kožních onemocnění.The novel 6α-methyl corticoids of the formula I according to the invention are therefore suitable, in combination with carriers customary in galenical pharmacy, for the topical treatment of contact dermititis, eczema of all kinds, neurodermatoses, erythrodermia, burns, itchy vulva and anus, , psoriasis, flat red and flounder lichen and similar skin diseases.
Tato speciální léčiva se vyrábějí obvyk248730 lým způsobem tím, že se účinné látky s vhodnými přísadami převedou v požadované aplikační formy, jako jsou například roztoky, pleťové vody, masti, krémy nebo náplasti. V takto formulovaných léčivech závisí koncentrace účinné látky na aplikační formě. U pleťových vod a mastí se výhodně používá koncentrace účinné látky v rozmezí 0,001 až 1 %.These special medicaments are manufactured in the usual manner by converting the active ingredients with suitable additives into the desired dosage forms, such as solutions, lotions, ointments, creams or patches. In such formulations, the concentration of active ingredient depends on the dosage form. For lotions and ointments, a concentration of active compound in the range of 0.001 to 1% is preferably used.
Kromě toho se nové sloučeniny, vyrobené způsobem podle vynálezu, popřípadě v kombinaci s obvyklými nosiči a pomocnými látkami, dobře hodí i k výrobě inhalačních prostředků, kterých je možno použít k léčení alergických onemocnění dýchacích cest, jako je například bronchiální asthma nebo zánět nosní sliznice.In addition, the novel compounds produced by the process of the invention, optionally in combination with conventional carriers and excipients, are also well suited for the manufacture of inhalants which can be used to treat allergic respiratory diseases such as bronchial asthma or nasal mucositis.
Dále jsou nové kortikoidy vhodné pro aplikaci v podobě tobolek, tablet nebo dražé, které výhodně obsahují 10 až 200 mg účinné látky a užívají se orálně nebo v podobě suspenzí, které s výhodou obsahují 100 až 500 mg účinné látky v jedné dávkovači jednotce a aplikují se rektálně, a též pro léčení alergických onemocnění zažívacího traktu, jako je vředovitá kolitida nebo granulomatózní kolitida.Furthermore, the novel corticoids are suitable for administration in the form of capsules, tablets or dragees, which preferably contain 10 to 200 mg of active ingredient and are used orally or in the form of suspensions, preferably containing 100 to 500 mg of active ingredient per dosage unit and administered. rectally, and also for the treatment of allergic diseases of the digestive tract such as ulcerative colitis or granulomatous colitis.
Předmětem vynálezu je způsob výroby derivátů 6a-methylkortikoidů obecného vzorce I, který se vyznačuje tím, že se 6 a-methylkortikoid obecného vzorce IISUMMARY OF THE INVENTION The present invention provides a process for the preparation of 6α-methyl corticoid derivatives of the general formula I, characterized in that
ve kterém r:::://. a R mají výše uvedený význam, chloruje v poloze 21.in which r :::: //. and R are as defined above, chlorinating at position 21.
Podmínky výroby sloučenin podle vynálezu jsou popsány v některém z německých zveřejňovacích spisů DOS ě. 2 645 104,The conditions for the preparation of the compounds according to the invention are described in one of the German publications. 2,645 104,
645 105, 2 340 591, 1 958 549, US patentu č.645,105, 2,340,591, 1,958,549, U.S. Pat.
383 394, jakož i v J. Org. Chem. 38, 4 203 (1973). 'W??383,394 and in J. Org. Chem. 38, 4,203 (1973). 'W ??
Způsob podle vynálezu je blíže objasněn v dále uvedených příkladech provedení.The process according to the invention is explained in more detail in the following examples.
Příklad 1Example 1
a) Z roztoku 5,0 g 9a-chlor-ll(3,17a,21-trihydroxy-6a-methyl-l,4-pregnadien-3,20-dienu ia 0,5 g pyridiniumtosylátu ve 35 ml dimethylformamidu a 350 ml benzenu se při teplotě 130 °C oddestiluje přes odlučovač vody 150 ml benzenu. K reakčnímu roztoku se za horka pomalu přidá 10 ml triethylesteru kyseliny orthooctové, načež se oddestiluje další množství benzenu a jiné snadno těkavé reakční složky. Pak se přidají 4 ml pyridinu a směs se odpaří za sníženého tlaku do sucha. Izoluje se 9a-chlor-17 a,21-i (ethoxyethylidendioxy) -11/3-hydroxy-6a-methyl-l,4-pregnadien-3,20-dion v podobě oleje.(a) From a solution of 5,0 g 9a-chloro-11 (3,17a, 21-trihydroxy-6a-methyl-1,4-pregnadien-3,20-diene) and 0,5 g pyridinium tosylate in 35 ml dimethylformamide and 350 ml of benzene is distilled off at 150 DEG C. through a water separator with 150 ml of benzene, 10 ml of triethyl orthoacetic acid is slowly added to the reaction solution, and a further amount of benzene and other readily volatile reactants are distilled off. Evaporate to dryness under reduced pressure to isolate 9? -chloro-17?, 21? - (ethoxyethylidenedioxy) -1? 3-hydroxy-6? -methyl-1,4-pregnadien-3,20-dione as an oil.
b) Surový 9a-chlor-17a,21-(ethoxyethylidendioxy ) lla-hydr oxy-6a-methy 1-1,4-pregnadien-3,20-dion se rozpustí ve 150 ml methanolu a vzniklý roztok se míchá 1 hodinu při teplotě lázně 100 °C se směsí 54 ml 0,1 N kyseliny octové a 6 ml 0,1 M vodného roztoku octanu sodného. Pak se reakční směs zahustí na 1/3 svého objemu, přidá se voda a extrakty esteru kyseliny octové se promyjí do neutrální reakce. Po vysušení a zahuštění se surový produkt přečistí na 500 g silikagelu za použití směsí methylenchloridu a 0 až 20 % acetonu jako eluěních činidel. Získá se ze 4,6 g 17a-acetoxy-9a-chlor-ll(3,21-dihydroxy-6a-methyl-l,4-pregnadien-3,20-dionu o teplotě tání 216 až 218 °C.b) Crude 9α-chloro-17α, 21- (ethoxyethylidenedioxy) 11a-hydroxy-6α-methyl-1, 4-pregnadien-3,20-dione was dissolved in 150 mL of methanol and stirred at room temperature for 1 hour. bath at 100 ° C with a mixture of 54 ml of 0.1 N acetic acid and 6 ml of 0.1 M aqueous sodium acetate solution. The reaction mixture was then concentrated to 1/3 of its volume, water was added and the acetic acid ester extracts were washed until neutral. After drying and concentration, the crude product is purified on 500 g of silica gel using mixtures of methylene chloride and 0 to 20% acetone as eluents. It is obtained from 4.6 g of 17α-acetoxy-9α-chloro-11 (3,21-dihydroxy-6α-methyl-1,4-pregnadien-3,20-dione, m.p. 216-218 ° C).
Příklad 2 aj 5,0 g 17a,21-dihydroxy-6a-methyl-l,4,9(ll)-pregnatrien-3,20-dionu se nechá reagovat postupem popsaným v příkladu la s 10 ml triethylesteru kyseliny orthopropionové za vzniku 17a,21-(ethoxypropylidendioxy) -6a-methyl-l,4,9 (11) -pr egnatrien-3,20-dionu ve formě oleje.Example 2 and 5.0 g of 17a, 21-dihydroxy-6a-methyl-1,4,9 (11) -pregnatriene-3,20-dione were reacted as described in Example 1a with 10 ml of triethyl orthopropionate to give 17a. 21- (ethoxypropylidenedioxy) -6α-methyl-1,4,9 (11) -propylnatriene-3,20-dione as an oil.
bj Surový 17a,21-(ethoxypropylidendioxy) -6a-methyl-l,4,9 (lij -pregnatrien-3,20-dion se míchá 20 hodin za teploty lázně 80 QC se směsí 250 ml dimethylformamidu a 5 ml trimethylchlorsilanu. Potom se reakční směs odpaří do sucha a surový produkt se přečistí na 600 g silikagelu za použití směsi methylenchloridu s 0 až 12 % acetonu, jako eluěních činidel.bj crude 17a, 21- (ethoxypropylidendioxy) -6a-methyl-4,9 (ij -pregnatrien-3,20-dione is stirred for 20 hours at a bath temperature of 80 Q C with 250 ml of dimethylformamide and 5 ml of trimethylchlorosilane. Then The reaction mixture was evaporated to dryness and the crude product was purified on 600 g silica gel using methylene chloride / 0-12% acetone as eluents.
Výtěžek činí 3,5 g 21-chlor-6a-methyl-17a-pr opionyloxy-1,4,9 (11) -pregnatrien-3,20-dionu.The yield was 3.5 g of 21-chloro-6α-methyl-17α-propionyloxy-1,4,9 (11) -pregnatriene-3,20-dione.
Příklad 3Example 3
a) Postupem, obdobným postupu popsanému v příkladu la se 2,0 g 17a,21-dihydroxy-6a-methyl-l,4,9 (11 j-pr egnatrien-3,20-dionu nechají reagovat s triethylesterem kyseliny orthomáselné za vzniku 17a,21- (ethoxybutylidendioxy j -6a-methyl-l,4,9(llj-pregnatrien-3,20-dionu v podobě oleje.a) Following a procedure similar to that described in Example 1a, 2.0 g of 17α, 21-dihydroxy-6α-methyl-1,4,9 (11β-propynatriene-3,20-dione) was reacted with triethyl orthobutyrate to give 17α, 21- (ethoxybutylidenedioxy) -6α-methyl-1,4,9 (11β-pregnatriene-3,20-dione as an oil).
b) Na surový 17a,21-(ethoxybutylidendioxy ) -6a-methyl-l,4,9 (11 j -pregnatrien-3,20-dion se za podmínek popsaných v příkladu lb působí směsí 0,1 N kyseliny octové s 0,1 M roztokem octanu sodného, načež se reakční směs zpracuje a přečistí. Získá se 1,5 g 17a-butyryloxy-21-hydroxy-6a-methyl-1,4,9 (11 )-pregnatrien-3,20-dionu. Příklad 4(b) Crude 17α, 21- (ethoxybutylidenedioxy) -6α-methyl-1,4,9 (11β-prenatriene-3,20-dione was treated with 0.1 N acetic acid with 0.1 N acetic acid under the conditions described in Example 1b); The reaction mixture was worked up and purified to give 1.5 g of 17α-butyryloxy-21-hydroxy-6α-methyl-1,4,9 (11) -pregnatriene-3,20-dione. 4
a) Postupem popsaným v příkladu la se 5,0 g 17a,21-dihydroxy-6a-methyl-l,4,9(llj-pregnatrien-3,20-dionu nechá reagovat s 10 ml triethylesteru kyseliny orthobenzoové za vzniku 17a,21-(ethoxybenzylidendioxyj-6a-methyl-l,4,9(llj-pregnatrien-3,20-dionu, načež se reakční směs zpracuje obvyklým postupem.a) Following the procedure described in Example 1a, 5.0 g of 17a, 21-dihydroxy-6a-methyl-1,4,9 (11j-pregnatriene-3,20-dione) was reacted with 10 ml of triethyl orthobenzoate to give 17a, 21a. - (ethoxybenzylidenedioxy) -6a-methyl-1,4,9 (11j-pregnatriene-3,20-dione) and then working up in the usual manner.
b) Surový 17a,21-(ethoxybenzylidenoxy) -6a-methyl-l,4,9 (11 j -pregnatrien-3,20-dion se nechá reagovat za podmínek, popsaných v příkladu 3b, s trimethylchlorsilanem a vzniklý reakční produkt se zpracuje a přečistí. Izoluje se 3,2 g 17a-benzoyloxy-21-chlor-6«-methyl-l,4,9(ll)-pregnatrien-3,20-dionu.b) Crude 17α, 21- (ethoxybenzylidenoxy) -6α-methyl-1,4,9 (11β-pregnatriene-3,20-dione) was treated with trimethylchlorosilane under the conditions described in Example 3b and treated with the resulting reaction product. 3.2 g of 17α-benzoyloxy-21-chloro-6'-methyl-1,4,9 (11) -pregnatriene-3,20-dione is isolated.
Claims (1)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19823243482 DE3243482A1 (en) | 1982-11-22 | 1982-11-22 | NEW 6 (ALPHA) METHYL CORTICOIDS, THEIR PRODUCTION AND USE |
CS838675A CS248712B2 (en) | 1982-11-22 | 1983-11-22 | Production method of 6 alfa-methylcorticoids |
Publications (1)
Publication Number | Publication Date |
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CS248730B2 true CS248730B2 (en) | 1987-02-12 |
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ID=25746602
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Application Number | Title | Priority Date | Filing Date |
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CS8410073A CS248727B2 (en) | 1982-11-22 | 1984-12-20 | Production method of the 6alfa methylcorticoid derivatives |
CS8410075A CS248729B2 (en) | 1982-11-22 | 1984-12-20 | Production method of the 6alfa methylcorticoid derivatives |
CS8410074A CS248728B2 (en) | 1982-11-22 | 1984-12-20 | Production method of the 6alfa methylcorticoid derivatives |
CS8410076A CS248730B2 (en) | 1982-11-22 | 1984-12-20 | Production method of 6alfa methylcorticoid derivatives |
Family Applications Before (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CS8410073A CS248727B2 (en) | 1982-11-22 | 1984-12-20 | Production method of the 6alfa methylcorticoid derivatives |
CS8410075A CS248729B2 (en) | 1982-11-22 | 1984-12-20 | Production method of the 6alfa methylcorticoid derivatives |
CS8410074A CS248728B2 (en) | 1982-11-22 | 1984-12-20 | Production method of the 6alfa methylcorticoid derivatives |
Country Status (1)
Country | Link |
---|---|
CS (4) | CS248727B2 (en) |
-
1984
- 1984-12-20 CS CS8410073A patent/CS248727B2/en unknown
- 1984-12-20 CS CS8410075A patent/CS248729B2/en unknown
- 1984-12-20 CS CS8410074A patent/CS248728B2/en unknown
- 1984-12-20 CS CS8410076A patent/CS248730B2/en unknown
Also Published As
Publication number | Publication date |
---|---|
CS248728B2 (en) | 1987-02-12 |
CS248729B2 (en) | 1987-02-12 |
CS248727B2 (en) | 1987-02-12 |
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