Patent GB-937410-A (GB)
Title: Improvements in or relating to steroids and the manufacture thereof
IPC: C07J41/00
Filed: 1961-10-31
Abstract: The invention comprises compounds having the formulae: <FORM:0937410/IV(a)/1> wherein 'n' has a value of from 2-6, <FORM:0937410/IV(a)/2> represents <FORM:0937410/IV(a)/3> or <FORM:0937410/IV(a)/4> is oxygen or sulphur, W is <FORM:0937410/IV(a)/5> or <FORM:0937410/IV(a)/6> and X is <FORM:0937410/IV(a)/7> or <FORM:0937410/IV(a)/8> and wherein Ac is the acyl radical of a hydrocarbon carboxylic acid containing from 1-8 carbon atoms, provided that in formula (I), when n is 2, V is oxygen, Y is hydrogen and <FORM:0937410/IV(a)/9> represents <FORM:0937410/IV(a)/100> X does not represent <FORM:0937410/IV(a)/111> , N-oxides and mineral acid salts thereof wherein <FORM:0937410/IV(a)/122> , V, W and X are as above defined for all values of n from 2-6, and processes for the preparation thereof by treating a compound having the formula: <FORM:0937410/IV(a)/133> wherein R is an alkylene group with up to eight carbon atoms and wherein the carbon atoms attached to the oxygen bonds are separated by not more than one methylene group and V and Y have the same significance as in formula I (1) with an alkali metal metathetically acting agent and (2) with an alkyl chloride selected from compounds of the formula:  <FORM:0937410/IV(a)/144> wherein the parameters <FORM:0937410/IV(a)/155> and n are as defined above.  As alkali metal metathetically acting agent there may be used triphenylmethyl sodium or potassium, sodium or potassium hydrides or propyl or butyl lithium or sodium.  As alkyl chlorides there may be employed diethylaminoalkyl chloride or diethylamino alkyl chloride N-oxide wherein the alkyl group has 2-6 carbon atoms.  Suitable starting materials are 3b -hydroxy-5-androsten-17-one 17 ethylene ketal or 3b -mercapto-5-androsten-17-one 17-ethylene ketal.  If required a 17-keto group in the starting compound may be protected by ketalisation.  Subsequent to etherification the following reactions may be effected (1) catalytic hydrogenation to convert D 5-androstene 3-ethers to the corresponding saturated androstane 3-ether, (2) conversion of the 17b -hydroxyl group to a 17b -acyloxy group by esterification, (3) conversion of the 17-keto group with a Grignard to the 17b -hydroxy-17a -alkyl or ethynyl group, (4) conversion of the free tertiary amino steriod ether to its N-oxide, (5) reduction of the 17-keto group to obtain a 17b -hydroxy group by means of a metal hydride, e.g. lithium aluminium hydride, lithium borohydride, and potassium or sodium borohydride.ALSO:Hypocholesteremic compositions comprising a 3b  - (dialkylaminoalkoxy) - 5 - androsten - 17 - one, a 3b -(dialkylaminoalkoxy)-5a -androstan17-one, a 3b -(dialkylaminoalkoxy)-5-andro-sten-17-one N-oxide, a 3b -(dialkylaminoalkoxy) - 5a  - androstan - 17 - one N - oxide p  or a physiologically acceptable acid addition salt thereof, the said dialkylaminoalkoxy groups conforming to the formula <FORM:0937410/VI/1> wherein R is an alkyl group of less than 4 carbon atoms and n is an integer of 2-6, alone or with other hypocholesteremic agents such as 3,5,31-triiodothyronine, thyroxine type compounds such as sodium D- and L-thyroxine, glycocorticoids such as hydrocortisone, prednisolone and 6a  - methylprednisolone, anticoagulants such as heparin, 2-diphenylacetyl-1,3-indandione, polyethylene sulphonate and dicoumarol, vitamins such as nicotinic acid, Vitamin B12 and pyridoxine hydrochloride, oestrogens such as oestradiol, androgens such as testosterone, unsaturated fatty acids and esters such as corn oil and linoleic acid, antibiotics such as neomycin, analgesics such as aspirin, a -phenylbutyric acid and a -p-biphenylylbutyric acid, lipotrophic agents such as choline and inositol, amino acids such as taurine and glycine, sterols such as sitosterol, diuretics such as acetazolamide and chlorothiazide, anorexigenic agents such as amphetamine, or cardiovascular agents such as chlorisodiamine chloride, hexamethonium chloride and pentaerythritol tetranitrate, are administered as tablets, pills, capsules, powders, wafers, cachets, granules, sterile parenteral solutions or suspensions in aqueous or oil vehicles, and oral aqueous or oil dispersions, including syrups and elixirs.