CZ2009521A3 - 3alpha-Hydroxy-21xi, 22-oxide-21-homo-5alpha-pregnan-20-one, process if its preparation and its use - Google Patents

3alpha-Hydroxy-21xi, 22-oxide-21-homo-5alpha-pregnan-20-one, process if its preparation and its use Download PDF

Info

Publication number
CZ2009521A3
CZ2009521A3 CZ20090521A CZ2009521A CZ2009521A3 CZ 2009521 A3 CZ2009521 A3 CZ 2009521A3 CZ 20090521 A CZ20090521 A CZ 20090521A CZ 2009521 A CZ2009521 A CZ 2009521A CZ 2009521 A3 CZ2009521 A3 CZ 2009521A3
Authority
CZ
Czechia
Prior art keywords
homo
hydroxy
formula
pregnan
alpha
Prior art date
Application number
CZ20090521A
Other languages
Czech (cs)
Other versions
CZ302050B6 (en
Inventor
Kasal@Alexander
Budešínský@Miloš
Mareš@Pavel
Krištofíková@Zdena
Original Assignee
Ústav organické chemie a biochemie, Akademie ved CR, v.v.i.
Fyziologický ústav Akademie ved CR, v.v.i.
Psychiatrické centrum Praha
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ústav organické chemie a biochemie, Akademie ved CR, v.v.i., Fyziologický ústav Akademie ved CR, v.v.i., Psychiatrické centrum Praha filed Critical Ústav organické chemie a biochemie, Akademie ved CR, v.v.i.
Priority to CZ20090521A priority Critical patent/CZ302050B6/en
Publication of CZ2009521A3 publication Critical patent/CZ2009521A3/en
Publication of CZ302050B6 publication Critical patent/CZ302050B6/en

Links

Abstract

3.alfa.-Hydroxy-21.ksi.,22-oxido-21-homo-5.alfa.-pregnan-20-on vzorce II. Zpusob jeho výroby, který spocívá v Mannichove kondensaci formaldehydu a dimethylaminu, a rozkladu príslušného meziproduktu na 3.alfa.-hydroxy-21-homo-5.alfa.-pregn-21-en-20-on vzorce V, který se epoxiduje peroxidem vodíku v alkalickém prostredí. 3.alfa.-Hydroxy-21.ksi.,22-oxido-21-homo-5.alfa.-pregnan-20-on vzorce II se dále používá pro výrobu léciva urceného k predcházení a potlacení epileptických záchvatu.3.alpha.-Hydroxy-21, 22-oxido-21-homo-5.alpha.-pregnan-20-one of formula II. The method of its production, which consists of Mannich condensation of formaldehyde and dimethylamine, and the decomposition of the corresponding intermediate to 3.alpha.-hydroxy-21-homo-5.alpha.-pregn-21-en-20-one of formula V, which is epoxidized with peroxide hydrogen in alkaline medium. 3.alpha.-Hydroxy-21'-22-oxido-21-homo-5.alpha.-pregnan-20-one of formula II is further used for the manufacture of a medicament for preventing and suppressing epileptic seizures.

Description

3a-Hydroxy-2^,22-oxido-21-homo-5a-pregnan-20-on, způsob jeho výroby a jeho použití3a-Hydroxy-2 ', 22-oxido-21-homo-5a-pregnan-20-one, process for its production and use

Oblast technikyTechnical field

Tento vynález se týká 3a-hydroxy-21č,22-oxido-21-homo-5a-pregnan-20-onu, způsobu jeho výroby a jeho použití při potlačení epileptických záchvatů.The present invention relates to 3α-hydroxy-21β, 22-oxido-21-homo-5α-pregnan-20-one, to a process for its manufacture and to its use in the control of epileptic seizures.

Dosavadní stav technikyBACKGROUND OF THE INVENTION

Epileptické záchvaty jsou projevem náhlých elektrických impulsů projevujících se v části či celém mozku, pri němž může, ale nemusí dojít k poruše vědomí. Záchvat může být ztišen řadou látek, které tlumí přenos nervových signálů, jako jsou benzodiazepiny a barbituráty, které působí prostřednictvím receptoru γ-aminomáselné kyseliny (GABA). Nově může být tento receptor modulován i neurosteroidy typu allopregnanolonu vzorce IEpileptic seizures are a manifestation of sudden electrical impulses manifesting in part or all of the brain in which consciousness may or may not occur. The seizure may be attenuated by a number of substances that inhibit the transmission of nerve signals, such as benzodiazepines and barbiturates, which act via the γ-aminobutyric acid (GABA) receptor. Newly, this receptor can also be modulated by allopregnanolone type I neurosteroids

Tyto látky působí jako pozitivní allosterické modulátory GABA receptorů tím, že zvyšují proudy jak co do frekvence otevření iontového kanálu, tak i délky jeho otevření. Neurosteroidy tedy mohou být použity jako anestHetika, anxiolytika i látky s protikřečovým účinkem [Veleiro AS, Burton G. Structure-Activity Relationships of Neuroactive Steroids Acting on the GABA(A) Receptor. Curr Med Chem 2009;Jd:455-72] [Scaglione JB, Jastrzebska I, Krishnan K, Li P, Akk G, Manion BD, Benz A, Tailor A, Rath NP, Evers AS, Zorumski CF, Mennerick S, Covey DF. Neurosteroid analogues. 11. Alternativě ring systém scaffolds: gamma-aminobutyric acid receptor modulation and anesthetic actions of benz[f]indenes. JMed Chem 2006;49:4595-605], [Eisenman LN, Shu H-J, Akk G, Wang C, Manion BD, Kress GJ, Evers AS, Steinbach JH, Covey DF, Zorumski CF, Mennerick S. Anticonvulsant and anesthetic effects of a fluoresccnt neurosteroid analog activated by visible light. Nátuře Neurosci 2007,70:523-30],These substances act as positive allosteric modulators of the GABA receptors by increasing currents both in the frequency of opening of the ion channel and its length of opening. Thus, neurosteroids can be used as anesthetics, anxiolytics and antispasmodic agents [Veleiro AS, Burton G. Structure-Activity Relationships of Neuroactive Steroids Acting on the GABA (A) Receptor. Curr Med Chem 2009; Jd: 455-72] [Scaglione JB, Jastrzebska I, Krishnan K, Li P, Akk, Manion BD, Benz A, Tailor A, Rath NP, Zorumski CF, Mennerick S, Covey DF . Neurosteroid analogues. 11. Alternative ring system scaffolds: gamma-aminobutyric acid receptor modulation and anesthetic actions of benz [f] indenes. JMed Chem 2006; 49: 4595-605], Eisenman LN, Shu HJ, Akk G, Wang C, Manion BD, Kress GJ, Evers AS, Steinbach JH, Covey DF, Zorumski CF, Mennerick S. Anticonvulsant and anesthetic effects of and a fluorescent neurosteroid analog activated by visible light. Nature Neurosci 2007,70: 523-30],

Nevýhodou endogenního allopregnanoíonu (I) je, že se v těle rychle metabolizuje. Proto byla hledána analoga allopregnanoíonu, která byla založena na nejrůznějších modifikacích steroidního skeletu [Veleiro AS, Burton G. Structure-Activity Relationships of Neuroactive Steroíds Acting on the GABA(A) Receptor. Curr Med Chem 2009, 76:455-72].The disadvantage of endogenous allopregnanone (I) is that it metabolizes rapidly in the body. Therefore, allopregnanone analogs have been sought based on various modifications of the steroid skeleton [Veleiro AS, Burton G. Structure-Activity Relationships of Neuroactive Steroids Acting on the GABA (A) Receptor. Curr Med Chem 2009, 76: 455-72].

Nyní jsme překvapivě zjistili, že námi syntetizovaná nová sloučenina, 3a-hydroxy-2^,22oxido-21-homo-5a-pregnan-20-on vzorce IIWe have now surprisingly found that the novel compound we synthesized, 3α-hydroxy-2β, 22oxido-21-homo-5α-pregnan-20-one of formula II

(II) se váže na GABAa receptor in vitro a v souladu stím i potlačuje dva typy křečí indukovaných pentylen^etrazolem u potkanů srovnatelně s účinky ganaxolonu. Příprava látky vzorce II a její biologická aktivita je předmětem tohoto vynálezu.(II) binds to the GABAa receptor in vitro and, accordingly, suppresses two types of pentylene-etrazole-induced seizures in rats comparable to the effects of ganaxolone. The preparation of the compound of formula II and its biological activity is the object of the present invention.

Podstata vynálezuSUMMARY OF THE INVENTION

Tento vynález se týká 3a-hydroxy-2K,22-oxido-21-homo-5a-pregnan-20-onu vzorce IIThis invention relates to 3α-hydroxy-2K, 22-oxido-21-homo-5α-pregnan-20-one of formula II

(II),(II),

Dále se tento vynález týká syntézy 3a-hydroxy-21g22-oxido-2l-homo-5a-pregnarr20-onuFurthermore, the present invention relates to the synthesis of 3α-hydroxy-21g22-oxido-21-homo-5α-pregnarr20-one

II, která spočívá v tom, že se známý allopregnanolon vzorce III, characterized in that the known allopregnanolone of the formula I is known

se za podmínek Mannichovy kondensace převede na amin III,is converted to amine III under conditions of Mannich condensation,

· í' Λ <' x j *7 1 jehož;methobromid vzorce IV· '' Λ <' x j * 7 1 whose ; methobromide of formula IV

se rozloží na 21-homo-3a-hydroxy-5a-pregn-21-en-20-on vzorce Vis decomposed to 21-homo-3α-hydroxy-5α-pregn-21-en-20-one of formula V

který se oxiduje peroxidem vodíku na látkuwhich is oxidized by hydrogen peroxide to the substance

Tento vynález bude podrobněji ilustrován na následujících příkladech, které není možné brát jako omezení předloženého vynálezu, ale pouze jako jeho ilustraci.The present invention will be illustrated in more detail by the following examples, which are not to be construed as limiting the present invention but merely to illustrate it.

Příklady provedení vynálezuDETAILED DESCRIPTION OF THE INVENTION

Příklad 1Example 1

Výroba 3a-hydroxy-21£,22-oxido-21-homo-5a-pregnan-20-onu (II)Production of 3α-hydroxy-21α, 22-oxido-21-homo-5α-pregnan-20-one (II)

Roztok vodného peroxidu vodíku (33%, 2,0 mL) a hydroxidu sodného (4 N, 0.4 mL) v methanolu (8,0 mL) se přidá k roztoku olefinu V (150 mg, 0,45 mmol) ve směsi methanolu a THF (25 mL, 1:1) při 0 °C. Po 4 hodinách se rozpouštědlo částečně odpaří ve vakuu a produkt se vysráží přidáním nasyceného vodného roztoku chloridu sodného. Extrakce octanem ethylnatým poskytne bílé krystaly látky II (120 mg, 76 %). Tt 172-175 °C (aceton/heptan). [a]D +122 (CHClj, c 0,3). IR (CHCI3): 3616, 3489,1001 (OH); 3063 (epoxid); 1712 (OO). Pro C22H34O3 (346,5) vypočteno: 76.26 %C, 9.89 %H; nalezeno: 76,04 %C, 10.14 %H. Pro NMR spektrum, viz Tabulka 1.A solution of aqueous hydrogen peroxide (33%, 2.0 mL) and sodium hydroxide (4 N, 0.4 mL) in methanol (8.0 mL) was added to a solution of olefin V (150 mg, 0.45 mmol) in a mixture of methanol and THF (25 mL, 1: 1) at 0 ° C. After 4 hours the solvent was partially evaporated in vacuo and the product precipitated by addition of saturated aqueous sodium chloride solution. Extraction with ethyl acetate gave white crystals of compound II (120 mg, 76%). Mp 172-175 ° C (acetone / heptane). [α] D +122 (CHCl 3, c 0.3). IR (CHCl 3): 3616, 3489.1001 (OH); 3063 (epoxide); 1712 (OO). For C 22 H 34 O 3 (346.5) calculated: 76.26% C, 9.89% H; Found:% C, 76.04;% H, 10.14. For the NMR spectrum, see Table 1.

Příklad 2Example 2

Výroba 3a’Hydroxy-21-homo-5a-pregn-21-en-20-onu (V)Production of 3a’Hydroxy-21-homo-5a-pregn-21-en-20-one (V)

Allopregnanolon (I) byl podroben Mannichově reakci a rozkladu příslušné kvartémí amoniové base podle japonských autorů [Hikino H, Okuyama T, Arihara S, Hikino Y, Takemoto T, Mori H, Shibata K. Steroids. 24. Shidasterone, an insect metamorphosing substance fřom Blechnum-niponicum - structure. Chem Pharm Bull 1975;23:1458-79]. Látka V tvoří bílé krystaly, tt 153-154 °C (aceton/heptan). [a]o +127 (CHCI3, c 0.2). IR (CHCh): 3616,3479,1002 (OH); 1689,1664,1618,1609,986,960 (C=C-C=O). Pro C22H34O2 (330.5) vypočteno: 79,95 %C, 10.37 %H; nalezeno: 79,55 %C, 10,45 %H. NMR spektrum viz následující tabulka.Allopregnanolone (I) was subjected to Mannich reaction and decomposition of the respective quaternary ammonium base according to Japanese authors [Hikino H, Okuyama T, Arihara S, Hikino Y, Takemoto T, Mori H, Shibata K. Steroids. 24. Shidasterone, an insect metamorphosing substance of Blechnum-niponicum - structure. Chem Pharm Bull 1975; 23: 1458-79]. Compound V forms white crystals, mp 153-154 ° C (acetone / heptane). [α] D +127 (CHCl 3, c 0.2). IR (CHCl3): 3616,3479, 1002 (OH); 1689, 1664, 1618, 1609, 986,960 (C = C-C = O). For C 22 H 34 O 2 (330.5) calculated: 79.95% C, 10.37% H; Found:% C, 79.55;% H, 10.45. The NMR spectrum is as follows.

Tabulka 1 13C a lH NMR spektra popisovaných látek 13 C and 1 H NMR spectra of the compounds described

Pozice Position Olefin V Olefin V hlavní 53% [21/ř] main 53% [21 / ř] vedlejší 47% [215] 3CSecondary 47% [215] 3 C Epoxid II hlavní 53% [21Λ] Epoxy II main 53% [21Λ] 'H 'H vedlejší 47% [215] minor 47% [215] 13C 13 C *H * H 1 1 32,16 32.16 1,32; 1,46 1.32; 1.46 32,15 32.15 32,16 32.16 1,33;1,47 1.33, 1.47 2 2 28,98 28.98 1,63; 1,68 1.63; 1.68 28,97 28.97 1,63; 1,68 1.63; 1.68 3 3 66,52 66.52 4,05 4.05 66,49 66.49 4,05 4.05 4 4 35,83 35.83 1,38;1,51 1.38, 1.51 35,80 35.80 1,37;1,53 1.37, 1.53 5 5 39,09 39.09 1,55 1.55 39,04 39.04 39,06 39.06 -1,55 -1.55 6 6 28,43 28.43 -1,22 (2H) -1.22 (2H) 28,39 28.39 -1,22 (2H) -1.22 (2H) 7 7 31,99 31.99 0,97;l,69 0.97; 1.69 31,94 31.94 0,97; 1,68 0.97; 1.68 8 8 35,58 35.58 1,38 1.38 35,60 35.60 35,48 35.48 1,38 1.38 1,41 1.41 9 9 54,21 54.21 0,81 0.81 54,10 54.10 54,13 54.13 0,83 0.83 0,81 0.81 10 10 36,11 36,11 - - 36,09 36.09 36,11 36,11 - - -- - 11 11 20,76 20.76 1,25; 1,60 1.25; 1.60 20,71 20.71 20,75 20.75 1,27; 1,63 1.27; 1.63 12 12 39,27 39.27 1,38;1,89 1.38, 1.89 39,20 39.20 39,07 39.07 1,51;1,92 1.51, 1.92 l,46;2,04 1.46, 2.04 13 13 44,96 44.96 - - 45,78 45.78 45,55 45.55 -- - - - 14 14 57,00 57.00 1,22 1,22 56,85 56.85 56,87 56.87 1,23 1,23 15 15 Dec 24,51 24.51 1,22; 1,70 1.22; 1.70 24,58 24.58 24,48 24.48 l,23;l,7l 1,23; 1,71 16 16 22,67 22.67 1,64;2,27 1.64, 2.27 22,60 22.60 23,02 23.02 l,60;2,22 1.60, 2.22 l,70;2,18 1.70, 2.18 17 17 60,99 60.99 2,79 2.79 59,16 59.16 60,98 60.98 2,74 2.74 2,72 2.72 18 18 13,66 13.66 0,578 0.578 14,00 14.00 13,96 13.96 0,606 0.606 0,690 0.690 19 19 Dec 11,16 11.16 0,774 0,774 11,16 11.16 0,777 0,777 0,787 0,787 20 20 May 201,07 201.07 - - 207,60 207,60 207,18 207.18 - - -- - 21 21 137,11 137.11 6,42 6.42 53,27 53.27 52,41 52.41 3,46 dd 3,46 dd 3,52 dd 3,52 dd >17,4, 10,5 > 17.4, 10.5 >4,6,2,5 > 4,6,2,5 >4,4, 2,4 > 4.4, 2.4 22 22nd 127,05 127.05 5,67 dd, >10,5,1,5 5.67 dd, > 10.5, 1.5 46,21 46.21 47,11 47.11 2,76 dd,>6,4,2,5, 2,87 dd>6,7,2,4 2.76 dd, > 6,4,2,5, 2,87 dd > 6,7,2,4 6,20 dd, >17,4, 1,5 6.20 dd, > 17.4, 1.5 2,95 dd, >6,4,4,6 2,92 dd, >6,7,4,4 2.95 dd, > 6.4.4.6 2.92 dd, > 6.7.7.4

Příklad 3Example 3

AktivitaActivity

Látka II vykázala v GABAa receptorovém testu s použitím TBPS jako radioligandu tuto aktivitu: látka modulovala GABAa receptor s mohutností účinnosti IC50 = 50nM a efektivitou Imax = 40 %. Tento výsledek ukazuje, že tato sloučenina je účinná při ovlivňování stavů řízených inhibičními účinky γ-aminomáselné kyseliny, např. epileptických záchvatů.Compound II showed the following activity in the GABAa receptor assay using TBPS as a radioligand: the compound modulated the GABAa receptor with a potency of IC50 = 50nM and an efficacy of I max = 40%. This result shows that this compound is effective in influencing conditions controlled by the inhibitory effects of γ-aminobutyric acid, eg epileptic seizures.

Claims (3)

PATENTOVÉ NÁROKYPATENT CLAIMS 1. 3a-Hydroxy-21 ξ,22-οχΐάο-21 -homo-5a-pregnan-20-on vzorce II1. 3α-Hydroxy-21α, 22-οχΐάο-21 -homo-5α-pregnan-20-one of formula II 2. Způsob výroby sloučeniny o vzorci II podle nároku 1,vyznačující se tím, že se známý allopregnanolon vzorce I za podmínek Mannichovy kondensace převede na amin vzorce !IIr který se převede na N-methylbromid vzorce IV t- jenž se nechá rozložit na 21-homo-3a-hydroxy-5a-pregn-21-en-20-on vzorce V a 21-homo-3a-hydroxy-5a-pregn-21-en-20-on vzorce V se nechá zoxidovat peroxidem vodíku.2. A process for producing a compound of formula II according to claim 1, characterized in that the known allopregnanolone formula I under the conditions of the Mannich condensation converted to the amine of formula! II R which is converted to N-methyl bromide IV t - which was allowed to spread for 21 The homo-3α-hydroxy-5α-pregn-21-en-20-one of formula V and 21-homo-3α-hydroxy-5α-pregn-21-en-20-one of formula V are allowed to oxidize with hydrogen peroxide. 3. Použití 3a-hydroxy-2^,22-oxido-21-homo-5a-pregnan-20-onu vzorce II podle nároku 1 pro výrobu léčiva určeného k předcházení a potlačení epileptických záchvatů.The use of 3α-hydroxy-2,2,2-oxido-21-homo-5α-pregnan-20-one of formula II according to claim 1 for the manufacture of a medicament for preventing and suppressing epileptic seizures.
CZ20090521A 2009-08-04 2009-08-04 3alpha-Hydroxy-21xi, 22-oxide-21-homo-5alpha-pregnan-20-one, process if its preparation and its use CZ302050B6 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CZ20090521A CZ302050B6 (en) 2009-08-04 2009-08-04 3alpha-Hydroxy-21xi, 22-oxide-21-homo-5alpha-pregnan-20-one, process if its preparation and its use

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CZ20090521A CZ302050B6 (en) 2009-08-04 2009-08-04 3alpha-Hydroxy-21xi, 22-oxide-21-homo-5alpha-pregnan-20-one, process if its preparation and its use

Publications (2)

Publication Number Publication Date
CZ2009521A3 true CZ2009521A3 (en) 2010-09-15
CZ302050B6 CZ302050B6 (en) 2010-09-15

Family

ID=42727353

Family Applications (1)

Application Number Title Priority Date Filing Date
CZ20090521A CZ302050B6 (en) 2009-08-04 2009-08-04 3alpha-Hydroxy-21xi, 22-oxide-21-homo-5alpha-pregnan-20-one, process if its preparation and its use

Country Status (1)

Country Link
CZ (1) CZ302050B6 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CZ305837B6 (en) * 2015-02-25 2016-03-30 Vysoká škola chemicko - technologická v Praze (3{alpha}, 5{beta},20S)-3-Nitrooxy-pregnane-20-carboxylic acid

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3031444A (en) * 1960-01-22 1962-04-24 Pfizer & Co C 17beta-(2, 3-epoxidopropenoyl)-substituted androstenes
CH467761A (en) * 1965-07-19 1969-01-31 Hoffmann La Roche Process for the preparation of 1,2-epoxy-9B, 10a-steroids
US5232917A (en) * 1987-08-25 1993-08-03 University Of Southern California Methods, compositions, and compounds for allosteric modulation of the GABA receptor by members of the androstane and pregnane series
DK0752860T3 (en) * 1994-02-14 2000-11-13 Euro Celtique Sa Androstans and pregnans for allosteric modulation of GABA receptor
GR1003861B (en) * 2000-12-29 2002-04-11 Novel gabaa modulating neurosteroids

Also Published As

Publication number Publication date
CZ302050B6 (en) 2010-09-15

Similar Documents

Publication Publication Date Title
CELLA et al. Steroidal aldosterone blockers. II1
DE1618830B2 (en) Oxygen-containing llbeta-OB-13beta-C-gona-1, 3,5 (10&gt; trienes and process for their preparation
AU2014311148B2 (en) Vancomycin derivative, and preparation method and application thereof
DK165595B (en) 17-ANDROSTANCANCARBOXYLIC ACID ESTERS, PROCEDURES FOR THE PRODUCTION OF THEM AND PHARMACEUTICAL PREPARATION CONTAINING SAME AND USING THE SAME FOR THE PREPARATION OF A MEDICINE FOR THE TREATMENT OF FAILURE HEARTS
CZ2009521A3 (en) 3alpha-Hydroxy-21xi, 22-oxide-21-homo-5alpha-pregnan-20-one, process if its preparation and its use
NO802977L (en) NEW ISOCYANOIC ACID COMPOUNDS WITH SYSTOSTATIC EFFECTS AND PROCEDURES FOR THEIR PREPARATION
US3770780A (en) O-(nitroaryl)oximes of 3-keto steroids
US3200114A (en) 17-tetrahydropyranyl ethers of (3, 2-c)-pyrazole and (2, 3-d)-isoxazole derivatives o the androstane and 19-norandrostane series
EP1951738A2 (en) Further crystalline forms of rostafuroxin
Weier et al. 7. alpha.-Carboalkoxy steroidal spirolactones as aldosterone antagonists
EP0289451B1 (en) 3-Methylene-androst-4-en-17-ones, process for their preparation and pharmaceutical compositions containing them
US3459739A (en) 3 - spiro - 3&#39; - diaziridine- and -3&#39;-diazirinederivatives of the androstane and estrane series
US3686237A (en) O-(nitroaryl)oximes of 3-keto steroids
EP1594886B1 (en) Antitumoral d-homoestra-1, 3, 5 (10)-trien-3-yl 2-substituted sulfamates
US3214447A (en) 2alpha-methyl-11-oxygenated androstanes and intermediates therefor
US3153063A (en) 16-methyl-17-amino-androstane
US2446538A (en) 3-amino steroids and their preparation
US3158607A (en) 17-tetrahydropyranyl ethers of 2-methyl, 3-keto androstanes
DE1593524C3 (en)
US3862193A (en) O-(nitroaryl) oximes of 3-keto steroids
US3530179A (en) Condensation products of tetracyclines containing sulfur
FI84834C (en) Process for the preparation of therapeutically useful steroid derivatives of the androstancer series
US3461142A (en) 3-desoxy-pregnenes
SU1072447A1 (en) A-nor-3-aza-chloroacetyl-5b-cholestane displaying antitumor activity
AU2002342625B8 (en) Methylene-4-azasteroids

Legal Events

Date Code Title Description
MM4A Patent lapsed due to non-payment of fee

Effective date: 20190804