US3818055A - 17-(aralkylaminoalkyl)androstan-3b-ols, 5 derivatives thereof, ethers and esters corresponding - Google Patents

17-(aralkylaminoalkyl)androstan-3b-ols, 5 derivatives thereof, ethers and esters corresponding Download PDF

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US3818055A
US3818055A US00229206A US22920672A US3818055A US 3818055 A US3818055 A US 3818055A US 00229206 A US00229206 A US 00229206A US 22920672 A US22920672 A US 22920672A US 3818055 A US3818055 A US 3818055A
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cholesterol
derivatives
aralkylaminoalkyl
ols
androstan
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R Counsell
M Lu
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University of Michigan
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of only two carbon atoms, e.g. pregnane derivatives

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  • ABSTRACT Novel compositions containing as the active ingredient certain steroids containing an oxa or aza side chain at the l7-position possess anti-hyperadreno corticism activity as evidenced by their ability to inhibit the side-chain cleavage of cholesterol, 'a key'step in the conversion of cholesterol to adrenal hormones.
  • N0 Drawings comprises compositions containing compounds 1 17 -(ARALKYLAMINOALKYL)ANDROSTAN-3B- OLS, 5 DERfvATwEs'TI-IEiilioF, ET'HfizS ANT) ESTERS CORRESPONDING wherein R is hydrogen or an alkyl or acyl group, R' is an alkyl or aralkyl side chain containing either one or two .oxygen or nitrogen atoms, and the dotted line represents an optional 5,6-double bond.
  • a preferred embodiment of this invention comprises compositions containing compounds of the following formula wherein R is as defined hereinbefore and the dotted line represents an optional 5,6-double bond.
  • An additional preferred embodiment of this invention is the method of administering to mammals a composition as defined hereinbefore for the purpose of treating disease states resulting from hyperfunctioning adrenal glands.
  • alkyl groups are typi fied by those containing one-l8 carbon atoms, while the acyl groups are represented by the following formula wherein alkyl is as defined hereinbefore.
  • the aralkyl radicals denoted above are typified by the formula Alk--Ar wherein Alk is a bivalent alkylene radical containing one-l 8 carbon atoms and Ar represents an aryl radical as exemplified by phenyl, tolyl, xylyl, napthyl and the ring-substituted derivatives thereof.
  • compositions and methods of this invention are useful in view of their anti-hyperadrenocorticism activity as evidenced by their ability to inhibit the side-chain cleavage of cholesterol, a key step in the conversion of cholesterol to' adrenal hormones.
  • the adrenal glands are composed of two distinct parts, the cortex and the medulla. lt is thought that the saltand water-regulating hormones of the adrenals are produced in the outer zone of the cortex, i.e., the zona glomerulosa.
  • the cholesterol content of the adrenal cortex is normally very high.
  • the adrenal cortex is primarily concerned with the maintenance of homeostasis, the tendency toward stability in the normal body states of the organism. A large number of steroids are produced in the adrenal cortex, but the most important are hydrocortisone, corticosterone and aldosterone-Also formed are smaller quantities of estrogens, progesterone and weakly active androgens such as dehydroisoandosterone.
  • aldosterone The primary activity of aldosterone is the regulation of electrolyte and water changes; it is thus called a mineralocorticoid.
  • Hydro cortisone, on the other hand, regulates metabolic and tissue effects not associated with water and electrolyte balance; thus-is called a glucocorticoid.
  • the conversion of cholesterol in the adrenal cortex to the various steroid hormones produced therein is achieved by the action of a number of hydroxylating enzyme systems. Thus, cholesterol is first hydroxylated at the 20 or 22 position and those intermediates are further hydroxylated to afford 20,22-dihydroxycholesterol. Cleavage of that glycol by mitochondrial desmolase results in pregnenolone, which is then hydroxylated at various positions in the molecule to produce hormones such as hydrocortisone, aldosterone, corticosterone,
  • ous agents have been found to inhibit one or more of p s 8- the steps in the biosynthesis of adrenocortical hors? mones. This sub ect is discussed by Temple and Liddle, cholesterol s 10 2 i Ann. Rev. Pharmao, i0, 199 (1970).
  • One such agent ammglumhmde prcgnenolonc l()() 294 which has been studied extensively 1S aminoglutethimide. That substance has been shown to inhibit the I conversion of cholesterol to 20a-hydroxycholesterol.
  • Adrenal inhibitors may be used also as diagnostic ity of the instant compositions is illustrated further by agents.
  • aminoglutethimide as a therapeutic Rafed from 10 ml of P RY y i 20 0f agent is, however, severely limited by side effects such line and l g of Tween 80, dally for a Penod of 10 y as ataxia, anorexia and somnelence. Reversible non- A Similar group of live control animals is treated in the toxic goiters have also been reported in some cases. same way with the vehicle alone.
  • the plasma cortico- The ability of the instant compositions to inhibit the sterone levels are measured by the competitive protein side-chain cleavage of cholesterol is demonstrated by binding assay described by Murphy and Pattee, J. Clin. their activity-in the assay described by C. H.
  • compositions of this invention comprise one of the aforementioned TABLE l active ingredients combined with a pharmaceutically acceptable carrier. These compositions can be adminis- Concentration Percent tered either orally or parenterally.
  • aqueous solutions, non-aqueous l0 solutions or suspensions are appropriate for parenteral lzflmcholcsmul 100 I 8 administration.
  • therapeutically effective amount is defined as the amount of active ingredient that will produce an anti-hyperadrenocorticism effect.
  • amount of active ingredient that will produce an anti-hyperadrenocorticism effect.
  • the actual amount of active ingredient to be used will vary with the nature of the subject, the severity of the disease state, the route of administration and the particular active ingredient used.
  • 55 g. of 22-azacholesterol is sifted through a number 30 mesh screen, then is combined with 4,440 g. of terra alba, 937 g. of corn starch U.S.P. and 222 g. of polyvinylpyrrolidone.
  • Those ingredients are mixed, then are moistened with 200 ml. of isoproypl alcohol and the mixture is comminuted, then granulated with 1,100 ml. of isopropyl alcohol. That mixture is comminuted and dried at 140 F. for 4 hours.
  • 62 g. of magnesium steareate is added and the mixture is extruded through a 9.52 mm. dye to afford 20,000 tablets, each containing 25 mg. of 22-azacholesterol.
  • the compounds used in the novel compositions of this invention are manufactured by various methods which are well known in the art.
  • compounds with an oxa and oxa-aza side chain can be produced by methods described by lrmscher et al. in Steroids, 7, 557(1966).
  • the compounds with aza side chains may be prepared by treating the appropriate amine with the appropriate ketone or aldehyde and then reducing the product with a reducing agent such as sodium borohydride toafford the desired aza derivatives.
  • a reducing agent such as sodium borohydride
  • ZOa-aminopregn-5-en'3B-ol is refluxed with isobutyl aldehyde is methanol and the product reduced with so-.
  • dium borohydride to yield ZOa-isobutylaminopregn-S- en-3/3-ol.
  • an appropriate amine may be acylated with an appropriate acid chloride to yield the amide. Then the amide is contacted with a reducing agent such as lithium aluminum hydride to yield the amine.
  • a reducing agent such as lithium aluminum hydride.
  • the above reaction sequence is illustrated by the treatment of 2Oa-aminopregn-5-en-3,8-01 3-tetrahydropyranyl ether with 4-methylvaleryl chloride to yield the crude amide. Reduction of the amide with lithium aluminum hydride affords 20a-isohexylaminopregn5-en-3B-ol.

Abstract

Novel compositions containing as the active ingredient certain steroids containing an oxa or aza side chain at the 17-position possess anti-hyperadreno corticism activity as evidenced by their ability to inhibit the side-chain cleavage of cholesterol, a key step in the conversion of cholesterol to adrenal hormones.

Description

United States Patent 1191 Counsell et al.
[ June 18, 1974 l l7-( ARALKYLAMINOALKYL )ANDROS- TAN-3B-OLS, 5 DERIVATIVES THEREOF, ETHERS AND ESTERS CORRESPONDING [75] Inventors: Raymond E. Counsel]; Matthias C.
H. Lu, both of Ann Arbor, Mich.
[73] Assignee: The Regents of the University of Michigan, Ann Arbor, Mich.
[22] Filed: Feb. 24, 1972 211 App]. No; 229,206
[52] U.S. Cl. 260/397.5, 424/238 [51] Int. Cl. C07c 169/32 [58] Field of Search /Machine Searched Steroids [56] References Cited UNITED STATES PATENTS 3,262,853 7/1966 Bertin et al. 167/65 Primary Examiner'Henry A. French I Attorney, Agent, or FirmElliot N. Schubert 5 7] ABSTRACT Novel compositions containing as the active ingredient certain steroids containing an oxa or aza side chain at the l7-position possess anti-hyperadreno =corticism activity as evidenced by their ability to inhibit the side-chain cleavage of cholesterol, 'a key'step in the conversion of cholesterol to adrenal hormones.
3 Claims, N0 Drawings comprises compositions containing compounds 1 17 -(ARALKYLAMINOALKYL)ANDROSTAN-3B- OLS, 5 DERfvATwEs'TI-IEiilioF, ET'HfizS ANT) ESTERS CORRESPONDING wherein R is hydrogen or an alkyl or acyl group, R' is an alkyl or aralkyl side chain containing either one or two .oxygen or nitrogen atoms, and the dotted line represents an optional 5,6-double bond. Equivalent to the amines encompassed by the foregoing formula are the corresponding pharmaceutically acceptable non-toxic acid addition and quaternary salts as typified by the citrate, tartrate, maleate, ascorbate, gluconate, lactate, succinate, phosphate, sulfate, hydrobromide, hydrochloride, -metho=bromide, methochloride, methosulfate, ethosulfate. etc.
A preferred embodiment of this invention comprises compositions containing compounds of the following formula wherein R is as defined hereinbefore and the dotted line represents an optional 5,6-double bond.
An especially preferred embodiment of this invention of the foregoing formula whereinR' is a HAD-NH-alkyl and the dotted line represents an optional 5,6-double I radical and there is present a 5,6-double bond.
An additional preferred embodiment of this invention is the method of administering to mammals a composition as defined hereinbefore for the purpose of treating disease states resulting from hyperfunctioning adrenal glands.
In the foregoing formulas the alkyl groups are typi fied by those containing one-l8 carbon atoms, while the acyl groups are represented by the following formula wherein alkyl is as defined hereinbefore. The aralkyl radicals denoted above are typified by the formula Alk--Ar wherein Alk is a bivalent alkylene radical containing one-l 8 carbon atoms and Ar represents an aryl radical as exemplified by phenyl, tolyl, xylyl, napthyl and the ring-substituted derivatives thereof.
The compositions and methods of this invention are useful in view of their anti-hyperadrenocorticism activity as evidenced by their ability to inhibit the side-chain cleavage of cholesterol, a key step in the conversion of cholesterol to' adrenal hormones.
In mammals the adrenal glands are composed of two distinct parts, the cortex and the medulla. lt is thought that the saltand water-regulating hormones of the adrenals are produced in the outer zone of the cortex, i.e., the zona glomerulosa. The cholesterol content of the adrenal cortex is normally very high. The adrenal cortex is primarily concerned with the maintenance of homeostasis, the tendency toward stability in the normal body states of the organism. A large number of steroids are produced in the adrenal cortex, but the most important are hydrocortisone, corticosterone and aldosterone-Also formed are smaller quantities of estrogens, progesterone and weakly active androgens such as dehydroisoandosterone. The primary activity of aldosterone is the regulation of electrolyte and water changes; it is thus called a mineralocorticoid. Hydro=cortisone, on the other hand, regulates metabolic and tissue effects not associated with water and electrolyte balance; thus-is called a glucocorticoid. The conversion of cholesterol in the adrenal cortex to the various steroid hormones produced therein is achieved by the action of a number of hydroxylating enzyme systems. Thus, cholesterol is first hydroxylated at the 20 or 22 position and those intermediates are further hydroxylated to afford 20,22-dihydroxycholesterol. Cleavage of that glycol by mitochondrial desmolase results in pregnenolone, which is then hydroxylated at various positions in the molecule to produce hormones such as hydrocortisone, aldosterone, corticosterone,
ous agents have been found to inhibit one or more of p s 8- the steps in the biosynthesis of adrenocortical hors? mones. This sub ect is discussed by Temple and Liddle, cholesterol s 10 2 i Ann. Rev. Pharmao, i0, 199 (1970). One such agent ammglumhmde prcgnenolonc l()() 294 which has been studied extensively 1S aminoglutethimide. That substance has been shown to inhibit the I conversion of cholesterol to 20a-hydroxycholesterol. I The cholesterol Slde f l 3? Adrenal inhibitors may be used also as diagnostic ity of the instant compositions is illustrated further by agents. It has thus been found that aminoglutethimide the 5 blood Comcosterone followmg reduced the aldosterone secretion rate in patients with admmlstrmlon to rats of the represenmuve compolind primary aldosteronism. This property could thus be fi-azacholestewt in that 3 fivefemalle g used to establish whether or not there would be a benemg 1604 80 8- are G r peritonea ly with 5 mg. ficial effect from surgical removal of the adrenal of zz'azacholesterol 0375 i an emulslon glands. The use of aminoglutethimide as a therapeutic Rafed from 10 ml of P RY y i 20 0f agent is, however, severely limited by side effects such line and l g of Tween 80, dally for a Penod of 10 y as ataxia, anorexia and somnelence. Reversible non- A Similar group of live control animals is treated in the toxic goiters have also been reported in some cases. same way with the vehicle alone. The plasma cortico- The ability of the instant compositions to inhibit the sterone levels are measured by the competitive protein side-chain cleavage of cholesterol is demonstrated by binding assay described by Murphy and Pattee, J. Clin. their activity-in the assay described by C. H. Doering, Endocr., 24, 919 (1964). Included in the following Methods in Enzymology, Volume XV, page 591, Acatable for comparison purposes is data obtained for rats demic Press, New York (1969). That assay depends treated with aminoglutethimide, as reported by Gaunt upon inhibition of the enzymatic action of the mytoet al., EndocrinoL, 87, 1088 (1970).
TABLE II Compound Dose Blood Corticostcronc Level Percent Decrease Control Treated 22aza= 5 mg, 500 ng/ml (mean) 230 ng/ml 54 cholesterol each day 375 ng/ml (median) (mean) for l0 l87.5 ng/ml 50 days (median) aminoglu= I00 mg/ 713 ng/ml 275 rigiml 72.4 tcthimidc kg/day 50 mg/ 185 ng/ml I39 ng/ml 24 9 kg/day chondrial fraction of bovine adrenal cortex on'choles- The instant compositions can be administered in a terol7a H,26-C. The loss by volatilization of one dose range of about l-l ,000 mg/day. From the foregoof the cleavage products, i.e., isocaproic acid-C, seen ing in vitro and in vivo data it is estimated that 22- as a change in isotope ratios, is a direct measure of en- 40 azacholesterol is about 10 times as potent as aminogluzymatic activity, thus of side-chain cleavage. In that tethimide, thus should be administered at a preferred assay the results shown in the following table are obdose of about lOO mg./day. mi d, The novel anti-hyperadrenocorticism compositions of this invention comprise one of the aforementioned TABLE l active ingredients combined with a pharmaceutically acceptable carrier. These compositions can be adminis- Concentration Percent tered either orally or parenterally. For oral administration tablets, lozenges, capsules, dragees, pills or pow- I00 ders are suitable, while aqueous solutions, non-aqueous l0 solutions or suspensions are appropriate for parenteral lzflmcholcsmul 100 I 8 administration. Acceptable pharmaceutical carriers are 10 87.7 exemplified by gelatin capsules, sugars such as lactose or sucrose, starches such as corn starch or potato 01 ,9 starch, cellulose derivatives such as sodium carboxyg'umchtlcmml 3 methyl cellulose, ethyl cellulose, methyl cellulose or 30.35 dial: 100 cellulose acetate phthalate, gelatin, talc, calcium phoscholesterol l0 l phate such as dicalcium phosphate or tricalcium phos- 2 2.25-diuza= 100 69.7 t cholcsmml m 225 phate, sodium sulfate, calcium sulfate, polyvinylpyr- 22-azuhomo= 100 100 rolidone, acacia, polyvinyl alcohol, stearic acid, alka- 100 line earth metal stearates such as m t 1 50s agnesium s earate, 0.1 14.7 vegetable oils such as peanut Oll, cottonseed Oll, sesame 9 :3 3g 3 oil, olive oil, corn oil or theobroma, water, agar, alginic ,1 acid, benzyl alcohol, isotonic saline and phosphate bufier solutions as well as other non-toxic compatible 22-azab|snor= l()() 7 l .9 cholcsmml 20.3 substances used in pharmaceutical formulations. ZO-cthylaminopregm IOU 87.6 The instant method for producing an anti- ;bf;gf 8 53:3 hyperadrenocorticism response in mammals comprises S-en-JB-ol H) 30.0
administration of an instant novel composition containing a therapeutically effective amount of the active ingredient. The term therapeutically effective amount is defined as the amount of active ingredient that will produce an anti-hyperadrenocorticism effect. For a particular subject the actual amount of active ingredient to be used will vary with the nature of the subject, the severity of the disease state, the route of administration and the particular active ingredient used.
The preparation of a representative composition suitable for oral administration is described as follows.
55 g. of 22-azacholesterol is sifted through a number 30 mesh screen, then is combined with 4,440 g. of terra alba, 937 g. of corn starch U.S.P. and 222 g. of polyvinylpyrrolidone. Those ingredients are mixed, then are moistened with 200 ml. of isoproypl alcohol and the mixture is comminuted, then granulated with 1,100 ml. of isopropyl alcohol. That mixture is comminuted and dried at 140 F. for 4 hours. 62 g. of magnesium steareate is added and the mixture is extruded through a 9.52 mm. dye to afford 20,000 tablets, each containing 25 mg. of 22-azacholesterol.
The compounds used in the novel compositions of this invention are manufactured by various methods which are well known in the art. For example, compounds with an oxa and oxa-aza side chain can be produced by methods described by lrmscher et al. in Steroids, 7, 557(1966).
The compounds with aza side chains may be prepared by treating the appropriate amine with the appropriate ketone or aldehyde and then reducing the product with a reducing agent such as sodium borohydride toafford the desired aza derivatives. Typically, ZOa-aminopregn-5-en'3B-ol is refluxed with isobutyl aldehyde is methanol and the product reduced with so-. dium borohydride to yield ZOa-isobutylaminopregn-S- en-3/3-ol.
Alternatively, an appropriate amine may be acylated with an appropriate acid chloride to yield the amide. Then the amide is contacted with a reducing agent such as lithium aluminum hydride to yield the amine. The above reaction sequence is illustrated by the treatment of 2Oa-aminopregn-5-en-3,8-01 3-tetrahydropyranyl ether with 4-methylvaleryl chloride to yield the crude amide. Reduction of the amide with lithium aluminum hydride affords 20a-isohexylaminopregn5-en-3B-ol.
The methods of preparation of the compounds employed in this invention will appear more fully from the examples which follow. In those examples temperatures are given in degrees Centigrade (C.) and quantities of material in parts by weight unless parts by volume is specified.
' EXAMPLE 1 A solution of 0.500 part of 20a-aminopregn-5-en-3B- o] and three parts of isobutyl aldehyde in 40 parts of absolute methanol is refluxed for 2 hours on a steam bath. Then the reaction mixture is allowed to cool to room temperature and three parts of sodium borohydride is added to the stirred mixture, portionwise over a 30 minute period, at a temperature of about -20. After that addition is completed, stirring is continued for an additional 2 hours. Then eight parts of acetone is added to destroy the excess sodium borohydride and the reaction mixture is poured into ice water. The precipitate which forms is collected by filtration, washed with water and allowed to dry. Recrystallization of the crude product from acetone-water affords pure a- 6 isobutylaminopregn-S-en3B-ol (2 2aazanorcholesterol), melting at about 128l30 and displaying an optical rotation of about 34.5.
EXAMPLE 2 Substitution of equivalent quantities of formaldehyde, acetaldehyde, dimethyl ketone and isoamyl- =aldehyde in the procedure of Example 1, affords, respectively, ZOa-methylaminopregn-S-en-3B-ol, 20aethylaminopregn-5-en-3B-ol, 20aisopropylaminopregn-S-en-3,8-01 20aisoamylaminopregn-5-en-3/3-ol.
EXAMPLE 3 To a stirred solution of 0.500 part of 20a-aminopregn-5-en-3B-ol S-tetrahydropyranyl ether in 17.6 parts of benzene is added dropwise a solution of 0.840 part of 4-methylvaleryl chloride in 8.8 parts of benzene. The mixture is stirred at room temperature for 24 hours and then is poured into ice water. The organic phase is separated, washed successively with water and 5 percent sodium bicarbonate solution, dried over anhydrous sodium sulfate and filtered. The filtrate is evaporated under reduced pressure to afford the crude amide. Then 0.60 part of the crude amide is dissolved in 26 parts of hot dioxane and that solution is added dropwise to a refluxing slurry comprised of 0.500 part of lithium aluminum hydride in 78 parts of dioxane. The mixture is refluxed and stirred for 20 hours whereupon the excess hydride is decomposed by the successive dropwise addition of 40 parts by volume of a l :4 water-dioxane solution, five parts by volume of a 25 percent sodium hydroxide solution and five parts of water. The mixture is filtered to remove the inorganic salts, which are washed on the filter with dioxane, and then the filtrate is evaporated to dryness. The remaining material is dissolved in cther and hydrogen chloride gas is added to the solution. The hydrochloride salt which precipitates is collected by filtration and treated with potassium carbonate to afford crude product. Recry-stallization of the crude product from acetone affords pure crystalline 20a-isohexylaminopregn- 5-en-3B-ol, melting at about 1 l3l 14 and displaying an optical rotation of about 26.6.
EXAMPLE 4v EXAMPLE .5
Substitution of an equivalent quantity of phenylaand cetyl chloride in the procedure of Example 3 affords 20a-phenethylaminopregn-5-en-3fl-ol.
EXAMPLE 6 By substituting equivalent quantities of 20a-aminopregnan-3B-ol 3-acetate and 3-phenylpropionyl chlor ide in the procedure of Example 3, there is produced 20a-( 3-phenylpropyl )aminopregnan-3B-ol 3-acetate.
EXAMPLE 7 Substitution of equivalent quantities of 20a-aminopregnan-3,B-ol 3-methyl ether and 3-phenylpropionyl chloride in the procedureof Example 3 affords 20a-(3- phenylpropyl)aminopregnan-IiB-ol 3-methyl ether.
EXAMPLE 8 When equivalent quantities of ZOa-aminopregnan- 3B-ol 3-propionate and 3-phenylpropionyl chloride are substituted in the procedure of Example 3, there is produced a-(3-phenylpropyl)aminopregnan-3B-ol 3- propionate.
EXAMPLE 9 Substitution of equivalent quantities of 20a-aminopregn-5-en-3B-ol 3-acetate and 3- phenylpropionyl chloride in the procedure of Example 3, yields 20a-( 3-phenylpr0pyl)aminopregn-5-en-3B-ol 3-acetate.
What is claimed is:
l. A compound of the formula H-NHAik-Q H I Q aC R O I LNHMPQ Roi wherein R is hydrogen or an alkyl or alkanoyl radical containing one to three carbon atoms and Alk represents an alkyl radical containing two to three carbon atoms.
3. As in claim 1, the compound which is 20aphenethylaminopregn-S-en-faB-ol.
t 7 UNITED STATES PATENT OFFICE v CERTIFICATE oT Patent No. 3 55 Dated June 18 197 4 Inventor(s) Raymond E. Counsell and Matthias c. H. Lu
It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:
In the title "BB" should be 36 ---5 ,5" should be ,A5
In the ab stract "anti-hyperadreno =corticism" should: be antihy peradrenocorticism Column 1, line 3 "metho-bromide" should b e methobromide Column 2, line 7, "one-l8" should be 17-18 Column -2",- line 17, "onel8" should be 1-18 Column 2 line 13, "hydro-cortisone" should be hydrocortisone Column 3, Table I, under compound entries, delete "l",
"0.1", "10'', "0.1" and "0.1", and move them laterally across to line up with concentration entries. I
Column 6, line 8, "=aldehyde" should be aldehyde Column 6, line il, "Recry-stallization" should be Recrystallization Signed and sealed this 3lst day of December 1974.
(SEAL) Attest:
TZCCDI 3 2. 5133?? C. I-LKRSPALL DANN Attesting Officer Commissioner of Patents DRM PC4050 (10-69) USCQMM'DC 60376-P69 & U.S4 GOVERNMENT PRINTING OFFICE: I969 0-366-334

Claims (2)

  1. 2. As in claim 1, a compound of the formula
  2. 3. As in claim 1, the compound which is 20 Alpha -phenethylaminopregn-5-en-3 Beta -ol.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993015104A1 (en) * 1992-01-29 1993-08-05 Research Corporation Technologies, Inc. 20-substituted pregnene derivatives and their use as androgen synthesis inhibitors

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3262853A (en) * 1963-01-16 1966-07-26 Roussel Uclaf Novel 20beta-amino-5beta-pregnanes

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3262853A (en) * 1963-01-16 1966-07-26 Roussel Uclaf Novel 20beta-amino-5beta-pregnanes

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993015104A1 (en) * 1992-01-29 1993-08-05 Research Corporation Technologies, Inc. 20-substituted pregnene derivatives and their use as androgen synthesis inhibitors

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