CS248727B2 - Production method of the 6alfa methylcorticoid derivatives - Google Patents
Production method of the 6alfa methylcorticoid derivatives Download PDFInfo
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- CS248727B2 CS248727B2 CS8410073A CS1007384A CS248727B2 CS 248727 B2 CS248727 B2 CS 248727B2 CS 8410073 A CS8410073 A CS 8410073A CS 1007384 A CS1007384 A CS 1007384A CS 248727 B2 CS248727 B2 CS 248727B2
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- methyl
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- methylcorticoid
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- 238000004519 manufacturing process Methods 0.000 title description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 239000005051 trimethylchlorosilane Substances 0.000 claims description 4
- 239000003470 adrenal cortex hormone Substances 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- RKHQGWMMUURILY-UHRZLXHJSA-N cortivazol Chemical compound C([C@H]1[C@@H]2C[C@H]([C@]([C@@]2(C)C[C@H](O)[C@@H]1[C@@]1(C)C2)(O)C(=O)COC(C)=O)C)=C(C)C1=CC1=C2C=NN1C1=CC=CC=C1 RKHQGWMMUURILY-UHRZLXHJSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 125000002092 orthoester group Chemical group 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- -1 ethoxyethylidenedioxy Chemical group 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 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
- 239000000203 mixture Substances 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 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
- FGWYWKIOMUZSQF-UHFFFAOYSA-N 1,1,1-triethoxypropane Chemical compound CCOC(CC)(OCC)OCC FGWYWKIOMUZSQF-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 239000012043 crude product Substances 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
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- KOPMZTKUZCNGFY-UHFFFAOYSA-N 1,1,1-triethoxybutane Chemical compound CCCC(OCC)(OCC)OCC KOPMZTKUZCNGFY-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
- 206010012442 Dermatitis contact 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
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 239000000654 additive Substances 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
- 230000015572 biosynthetic process Effects 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
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000002552 dosage form 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
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002905 orthoesters Chemical group 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 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
- 239000000243 solution Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009897 systematic effect Effects 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
- 210000003905 vulva Anatomy 0.000 description 1
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- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Vynález se týká způsobu výroby nových derivátů 6a-methylkortikoidu obecného vzorce Ib ií ·, /'•Λ’The present invention relates to a process for the preparation of novel 6α-methylcorticoid derivatives of the general formula (Ib).
OO
C..r/3 (f b) ve kterémC..r / 3 (fb) in which
-----: znamená jednoduchou nebo dvojnou vazbu,-----: means a single or double bond,
R‘ znamená alkylovou skupinu s nejvýše 7 atomy uhlíku nebo fenylovou skupinu aR‘ represents an alkyl group having at most 7 carbon atoms or a phenyl group and
X“ znamená hydroxyskupinu nebo atom chloru.X 'represents a hydroxy group or a chlorine atom.
Bylo zjištěno, že nové 6a-methylkortikoidy obecného vzorce Ib vyrobené způsobem podle vynálezu, mají při lokální aplikaci často významně silnější účinnost než až dosud známé 6a-methylkortikoidy. Tato účinnost je často dokonce ještě významněji silnější, než je účinnost dvojnásobně fluorovaných „ušlechtilých“ kortikoidů, jako je třeba 6a,9a-difluor-lljS-hydroxy-16a-methyl-21-valeryloxy-l,4-pregnadien-3,20-dion (tj. Nerisona).It has been found that the novel 6α-methyl corticoids of the general formula Ib produced by the process according to the invention often have significantly greater potency when applied topically than the hitherto known 6α-methyl corticoids. This potency is often even more potent than that of double-fluorinated "noble" corticoids such as 6α, 9α-difluoro-11β-hydroxy-16α-methyl-21-valeryloxy-1,4-pregnadien-3,20- dion (ie Nerison).
Při systematické aplikaci jsou tyto 6a-methylkortikoidy překvapivě často slaběji účinné než příslušné dosud známé 6a-methylkortikoidy.Surprisingly, in systematic administration, these 6α-methylcorticoids are often less potent than the corresponding 6α-methylcorticoids known to date.
Nové 6a-methylkortikoidy obecného vzorce Ib, vyrobené způsobem podle vynálezu, jsou proto vhodné v kombinaci s nosiči obvyklými v galenické farmacii k lokálnímu ošetření kontaktní dermatitidy, 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 general formula (Ib) produced by the process according to the invention are therefore suitable, in combination with carriers customary in galenical pharmacy, for topical treatment of contact dermatitis, eczema of various kinds, neurodermatoses, erythrodermia, burns, itchy vulva and anus; , psoriasis, flat red and flounder lichen and similar skin diseases.
Tato speciální léčiva se vyrábějí obvyklým 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 aplikač248727 ní formě. U pleťových vod a mastí se výhodně používá koncentrace účinné látky v rozmezí 0,001 až 1 °/o.These special medicaments are manufactured in conventional 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 application form. For lotions and ointments, a concentration of active compound in the range of 0.001 to 1% is preferred.
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 Ib, který se provádí tak, že se hydrolyticky nebo použitím trimethylchlorsilanu odštěpí orthoesterové seskupení kortikoidu obecného vzorce VSUMMARY OF THE INVENTION The present invention provides a process for the preparation of 6α-methyl corticoid derivatives of the formula Ib, which is carried out by cleaving the orthoester moiety of a corticoid of the formula V hydrolytically or using trimethylchlorosilane
ve kterém a R‘ mají výše uvedený význam ain which a R ‘is as defined above and
R“ znamená alkylový zbytek s 1 až 4 atomy uhlíku.R 'represents an alkyl radical having 1 to 4 carbon atoms.
Podmínky výroby sloučenin podle vynálezu jsou popsány v některém z německých zveřejňovacích spisů DOS čís. 2 645104, 2 645 105, 2 340 591, 1 958 569, US patentu č. 3 383 394, jakož i v J. Org. Chem. 38, 4 203 (1973).The conditions for the preparation of the compounds according to the invention are described in one of the German publication no. No. 2,645,104; 2,645,105; 2,340,591; 1,958,569; U.S. Patent No. 3,383,394; and in J. Org. Chem. 38, 4,203 (1973).
Způsob podle vynálezu je blíže objasněn v dále uvedených příkladech:The process according to the invention is illustrated 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-dionu a 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-17a,21- (ethoxyethylidendioxy)-11/3-hydroxy-6a-methyl-l,4-pregnadien-3,20-dion v podobě oleje.a) From a solution of 5.0 g of 9a-chloro-11 / 3,17a, 21-trihydroxy-6a-methyl-1,4-pregnadien-3,20-dione and 0.5 g of pyridinium tosylate in 35 ml of dimethylformamide and 350 ml of benzene at 130 ° C was distilled through a water separator with 150 ml of benzene. To the reaction solution, 10 ml of triethyl ortho-acetic acid is slowly added while hot, and a further amount of benzene and other readily volatile reactants are distilled off. Pyridine (4 ml) was added and the mixture was evaporated to dryness under reduced pressure. 9α-Chloro-17α, 21- (ethoxyethylidenedioxy) -11β-hydroxy-6α-methyl-1,4-pregnadien-3,20-dione is isolated as an oil.
b) Surový 9a-chlor-17a,21-(ethoxyethylidendioxy ) -ll/3-hydroxy-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 elučního činidla. Získá se 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) -1 H -methyl-6α-methyl-1, 4-pregnadien-3,20-dione was dissolved in 150 mL of methanol and stirred for 1 h at a bath temperature of 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 methylene chloride / 0-20% acetone as eluent. 4.6 g of 17α-acetoxy-9α-chloro-11β, 3,21-dihydroxy-6α-methyl-1,4-pregnadien-3,20-dione, m.p. 216-218 ° C, are obtained.
Příklad 2 aj Obdobným postupem jako v příkladu laj se nechají reagovat 2,0 g 9a-chlor-ll(S,17a,21-trihydroxy-6a-methyl-l,4-pregnadien-3,20-dionu s triethylesterem kyseliny orthopropionové za vzniku 9a-chlor-17a,21- (ethoxypΓopylidendl·oxy) -ll(Ž-hydroxy-6a-methyl-l,4-pregnadien-3,20-dionu v podobě oleje.Example 2 and 2.0 g of 9α-chloro-11 (S, 17α, 21-trihydroxy-6α-methyl-1,4-pregnadien-3,20-dione) are reacted with triethyl orthopropionate in a manner similar to Example 1a. formation of 9α-chloro-17α, 21- (ethoxy-propylidenedloxy) -11- (6-hydroxy-6α-methyl-1,4-pregnadien-3,20-dione as an oil).
bj Surový 9a-chlor-17a,21-(ethoxypropylidendioxy j -ll/3-hydroxy-6a-methyl-l,4-pregnadien-3,20-dion se nechá reagovat obdobně jako v příkladu 1b), načež se zpracuje a přečistí stejně, jak je popsáno v příkladu lbj. Izoluje se 1,6 g 9a-chlor-ll/í,21-dihydroxy-6a-methyl-17a-propionyloxy-l,4-pregnadien-3,20-dionu o teplotě tání 201 až 203°C.bj Crude 9α-chloro-17α, 21- (ethoxypropylidenedioxy) -1 H- 3 -hydroxy-6α-methyl-1,4-pregnadien-3,20-dione was reacted in analogy to Example 1b), then worked up and purified as described in Example 1bj. 1.6 g of 9? -Chloro-11?, 21-dihydroxy-6? -Methyl-17? -Propionyloxy-1,4-pregnadien-3,20-dione, m.p. 201-203 ° C, are isolated.
Příklad 3Example 3
a) 5,0 g 17a,21-dihydroxy-6a-methyl-l,4,9(11 )-pregnatrien-3,20-dionu se nechá reagovat postupem popsaným v příkladu laj s 10 ml triethylesteru kyseliny orthopropionové za vzniku 17a,21-(ethoxypropylidendioxy) -6a-methyl-l,4,9 (11 j -pr egnatrien-3,20-dionu ve formě oleje.(a) 5.0 g of 17α, 21-dihydroxy-6α-methyl-1,4,9 (11) -pregnatriene-3,20-dione are reacted as described in example 1aj with 10 ml of triethyl orthopropionate to give 17a, 21- (ethoxypropylidenedioxy) -6α-methyl-1,4,9 (11β-propynatriene-3,20-dione as an oil).
b) Surový 17a,21-(ethoxypropylidendioxy )-6a-methyl-l,4,9 (11 )-pregnatrien-3,20-dion se míchá 20 hodin za teploty lázně 80 °C se směsí 250 ml dimethyl'formamidu a 5 ml trimethylchlorsilanu. Potom se reakční směs odpaří do sucha a surový produkt se přečistí na 600 g silikagelu za použití směsí methylenchloridu s 0 až 12 % acetonu jako elučního činidla. Výtěžek činíb) The crude 17α, 21- (ethoxypropylidenedioxy) -6α-methyl-1,4,9 (11) -pregnatriene-3,20-dione was stirred for 20 hours at a bath temperature of 80 ° C with a mixture of 250 mL of dimethylformamide and 5 mL of methyl ester. ml trimethylchlorosilane. The reaction mixture is then evaporated to dryness and the crude product is purified on 600 g of silica gel using methylene chloride / 0-12% acetone as eluent. The yield is
3.5 g 21-chlor-6«-methyl-17a-propionyloxy-1,4,9 (11j -pregnatrien-3,20-dionu.3.5 g of 21-chloro-6'-methyl-17α-propionyloxy-1,4,9 (11'-pregnatriene-3,20-dione).
Příklad 4Example 4
a) Postupem obdobným postupu popsanému v příkladu la), se 2,0 g 17a,21-dihydr oxy-6a-methyl-l,4,9 (11)-pr egnatrien-3,20-dionu nechají reagovat s triethylesterem kyseliny orthomáselné za vzniku 17»,21- (ethoxybutylidendioxy) -6a-methyl-l,4,9(ll]-pregnatrien-3,20-dionu ve formě oleje.a) In a manner similar to that described in Example 1a), 2.0 g of 17α, 21-dihydroxy-6α-methyl-1,4,9 (11) -propylnatriene-3,20-dione was reacted with triethyl orthobutyrate. to yield 17 ', 21- (ethoxybutylidenedioxy) -6α-methyl-1,4,9 (11) -pregnatriene-3,20-dione as an oil.
b) Na surový 17«,21-( ethoxybutylidendioxy ) -6a-methyl-l,4,9 (11 ] -pregnatrien-3,20-dion se za podmínek popsaných v příkladu lb) působí směsí 0,1 N kyseliny octové a 0,1 M roztoku octanu sodného, načež se reakční směs zpracuje a přečistí. Získá seb) The crude 17α, 21- (ethoxybutylidenedioxy) -6α-methyl-1,4,9 (11) -pregnatriene-3,20-dione is treated with a mixture of 0.1 N acetic acid under the conditions described in Example 1b) and 0.1 M sodium acetate solution was then worked up and purified. It is obtained
1.5 g 17a-butyryloxy-21-hydroxy-6a-methyl-1,4,9(11) -pregnatrien-3,20-dionu.1.5 g of 17α-butyryloxy-21-hydroxy-6α-methyl-1,4,9 (11) -pregnatriene-3,20-dione.
Příklad 5 aj Postupem popsaným v příkladu la) se 5,0 g 17a,21-dihydroxy-6a-methyl-l,4,9(ll j-pregnatrien-3,20-dionu nechá reagovat s 10 ml triethylesteru kyseliny orthobenzoové za vzniku 17a,21-(ethoxybenzylidendioxy)-6a-methyl-l,4,9 (11 j-pregnatrien-3,20-dionu, načež se reakční směs zpracuje obvyklým postupem.EXAMPLE 5 aj Following the procedure described in Example 1a), 5.0 g of 17α, 21-dihydroxy-6α-methyl-1,4,9 (11β-pregnatriene-3,20-dione) was reacted with 10 mL of triethyl orthobenzoate to give 17α, 21- (ethoxybenzylidenedioxy) -6α-methyl-1,4,9 (11β-pregnatriene-3,20-dione) was then worked up in the usual manner.
b) Surový 17a,21-(ethoxybenzylidenoxy)-6a-methyl-l,4,9 (11 )-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 17«-benzoyloxy-21-chlor-6o!-methyl-l,4,9 (11) -pregnatrien-3,20-dionu.b) Crude 17α, 21- (ethoxybenzylidenoxy) -6α-methyl-1,4,9 (11) -pregnatriene-3,20-dione was reacted with trimethylchlorosilane under the conditions described in Example 3b and treated with the resulting reaction product. and purify. 3.2 g of 17'-benzoyloxy-21-chloro-6'-methyl-1,4,9 (11) -pregnatriene-3,20-dione is isolated.
Claims (1)
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Application Number | Priority Date | Filing Date | Title |
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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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CS248727B2 true CS248727B2 (en) | 1987-02-12 |
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ID=25746602
Family Applications (4)
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 After (3)
Application Number | Title | Priority Date | Filing Date |
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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 |
Country Status (1)
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CS (4) | CS248727B2 (en) |
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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
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CS248728B2 (en) | 1987-02-12 |
CS248729B2 (en) | 1987-02-12 |
CS248730B2 (en) | 1987-02-12 |
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