US2561378A - 20-dimethylamino-pregnenes and their quaternary halides - Google Patents
20-dimethylamino-pregnenes and their quaternary halides Download PDFInfo
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- US2561378A US2561378A US773526A US77352647A US2561378A US 2561378 A US2561378 A US 2561378A US 773526 A US773526 A US 773526A US 77352647 A US77352647 A US 77352647A US 2561378 A US2561378 A US 2561378A
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- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
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- C07J75/00—Processes for the preparation of steroids in general
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- An additional object is to produce tertiary dimethylamines in the steroid series.
- Still another object is to produce quaternary ammonium compounds in the steroid series.
- steroid amines containing an amino group either at the 17 position of the nucleus or in a group attached to the 17 position'of the nucleus may be converted to the dimethylamines by reductive methylation through treatment with formaldehyde and formic acid.
- R is the cyclopentanopolyhydrophenane threne nucleus, 3; equals 0 or 1, and.
- dimethylamines may be converted to the quaternary ammonium halide salts by treatment of the dimethyl tertiary amines with alkyl and aralkyl halides.
- These quaternary ammonium compounds are valuable in the synthesis of therapeutically active steroids.
- the dimethylamines in addition to their being useful for'the preparation of the quaternary ammonium compounds, may themselves prove to have valuable therapeutic properties since 'certain other steroid amines have been recorded in the literature as being 'bacteriostatic agents.
- These reactions involved in the reductivemethylation and formation of the quaternary ammonium salts may be illustrated by the following equations, employing typical amines of the steroid ser1es.
- the alkaline suspension was extracted .75 'A mixture of 3.59 g. of -3-acetoxy-5-ternorch01 enylamine, 8.57 g. of 90% formic acid and 35% aqueous formaldehyde solution was heated on the steam bath under reflux for four hours. The mixture was then-chilled, made basic with dilute sodium carbonate solution and extracted with ether. The ether extract was washed with water several times and-dried. The white crystalline residue remaining after removal of solvent was recrystallized from ether-petroleum ether. There resulted 2.1' g., first'crop, of crude 3-acetoxy-5- ternorcholenyldimethylamine. More of the amine may be obtained by concentration of the mother-liquor. The amine when purified by further recrystallization melts at 1845-1875 C.
- EXAMPLE VI 3 (a) ,12 (a) -diaoetoa:y-terncrcholanyldimethylamine
- the acid chloride was prepared from 7.2 g.v of 3(a) 12(a) -diacetoxy-bisnor-cholanic acid and 4.2 cc. of thionyl chloride in 20 cc. of dry benzene- 40 cc. of dry ether. After one hour the solvent .was removed and the acid chloride was dissolved in 130 cc. of acetone. This solution was treated, dropwise, at 0-5 C. with a solution of 2.3 g. of sodium azide in 10 cc. of water.
- EXAMPLE 2 3 -acetory-allo-temo1'ch0Zanyltrimethylammonium bromide .
- a solution of 0.5g. of S-acetoxy-allo-ternorcholanyldimethyla-mine in cc. of benzene was mixed with a solution of 5 g. of methyl bromide in 5 cc. of benzene. Themixture was refluxed for five hours. As heating-progressed the solution became cloudy and then a solid separated. After dilution with ether, the white solid was separated and washed well with ether.
- the product, 3 acetoxy allo ternorcholanyltrimethyl ammonium bromide weighed 0.4.- g. The material is quite soluble in methanol but may be recrystallized from a cold, concentrated solution.
- EXAMPLE XIII 3m micry-5-eticcholenyldimethylisoamylammonium bromide
- a solution of 1.0 g. of 3-hydroxy-5-androstenel7-dimethylamine in 10 cc. of isoamyl bromide was refluxed for one hour. After chilling the mixture was diluted with ether and the solid was filtered. The crystalline solid, 0.5 g., was poorly soluble in ether and slightly soluble in water. It may be recrystallized from methanol. This material, 3 hydroxy 5 etiocholenyldimethyl isoaznylammonium bromide does not meet below 250 C.
- EXAMPLE EJI 301) .12 0) -diucetorymorchoianylzfimethyiamine The *diacetoxyderivative from 20:0. g'. of desoxych-oiic acid was converted to the acid chloride with 13 cc. of thionyl chloride-in cc. of .dry benezene-ZOO cc. of dry -ether,and one :drop 10% pyridine in benzene. After one and onehalf hours the solvent was removed in vacuo and the crystalline acid chlorideidissolved in 400 cc. of distilled acetone. This solution was cooled to 5 C. and a solution containing 7.0 g.
- Pregnene compounds selected from the class consisting of 20-dimethy1amino-5-pregnenes and their quaternary ammonium halides other than quaternary ammonium fluorides.
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Description
Patented July 24, 1951 UNITED STATES PATENT OFFICE 20-DIMETHYLAMINO-PREGNENES AND THEIR QUATERNARY HALIDES Percy L. Julian, Maywood, and Helen C. Printy and Edwin W. Meyer, Chicago, 111., assignors to The Glidden Company, Cleveland, Ohio, a corporation of Ohio No Drawing. Application September 11, 1947, Serial No. 773,526
ficient means for the production of therapeutically active materials. Certain of the quaternary ammonium compounds have been found useful in steroid degradation, thus any method for the preparation of the tertiary dimethylamines is of value and, indeed, a method which possesses a certain degree of specificity is of considerable importance. Furthermore, it has been stated that quaternary ammonium halides of 7-amino-steroids could not be formed (H. Eckhardt, Ber., 71, 461 (1938)), but we have found that all amines studied by our methods have led to such'quaternary compounds.
It is accordingly an object of, the present invention to provide a method for the production of tertiary dimethylamines in the steroidseries.
A further object is to provide a method for the production of quaternary ammonium compounds in the steroid series.
Another-object is to produce quaternary am-' monium compounds from tertiary dimethylamines of the steroid series.
An additional object is to produce tertiary dimethylamines in the steroid series.
Still another object is to produce quaternary ammonium compounds in the steroid series.
Other objects will be apparent to those skilled in the art from the following description.
It has been found that steroid amines containing an amino group either at the 17 position of the nucleus or in a group attached to the 17 position'of the nucleus may be converted to the dimethylamines by reductive methylation through treatment with formaldehyde and formic acid. Thus, amines of the type where R is the cyclopentanopolyhydrophenane threne nucleus, 3; equals 0 or 1, and. where 1 equals 0 when as equals 0 and where 1/ equals 0, 1 or 2 when as equals 1, may all be readily methylated to compounds of the type l CH3 R (EH (CH2),,N\ I l 2 CH3 above, and, converted to the quaternary ammonium derivatives of the type where R, x, and y are as previously designated and where R is alkyl or aralkyl and Z is chlorine, bromine, iodine or hydroxyl. This type of methylation is not sufficiently drastic to cause any extensive or uncertain alteration of other labile functional groups. These dimethylamines may be converted to the quaternary ammonium halide salts by treatment of the dimethyl tertiary amines with alkyl and aralkyl halides. These quaternary ammonium compounds are valuable in the synthesis of therapeutically active steroids. The dimethylamines, in addition to their being useful for'the preparation of the quaternary ammonium compounds, may themselves prove to have valuable therapeutic properties since 'certain other steroid amines have been recorded in the literature as being 'bacteriostatic agents. These reactions involved in the reductivemethylation and formation of the quaternary ammonium salts may be illustrated by the following equations, employing typical amines of the steroid ser1es.
(1) CH: CH3
CH; CH: OHa RAJ-NH: H( N I CH3 CH3 ECHO HCOOH HO lRX CH3 CH HNCH3 CH3 (2) CH CH C113 CH3 R N112 N CH3 on, on3
H030 RX HCOOH HO 110- I (3) CH3 I CH3 CH3 CH: I CH3 CH3 $11 I CH3 C I II /OH3 Ac? A3HCE2NH2 AGO CH-CHz-N I AcO 'C'H-CH2.N CH
I l A -CH: R
HOHO v v L I I II ncoon I AC0 I and v (4) CH3 7 CH3 I H3 CH3 (EH3 CH3 CH3 CH3' CE; I I
A09 CHCH2 CH2-NH2 AcO H-CHz-OHz-N A09 H-CH'z-CHz-IQ-CHgl l i 0113 f I X R HCHO HCOOH AcO-- AoO- EXAMPLE I with ether and the ether layer was washed several I times with water and dried. The ethereal .solu '3'hydmmy'5'tamOmhozem/ldlmemylamme tion was concentrated to about 30 go. volume, 6.34 g. of 3-hydroxy 5-ternorcholeny1amine was 65 n and the crystalline Solid separated by m dissolved with gentle Warming in 624 of 90% tratlon. A second crop of orystallme materialformic acid. After the addition of 3.77 g. of 35 was tamed by concentratlon of motheraqueous formaldehyde solution, the mixture was hquor' The P dw refluxed for four hours. C02 was liberated during nomholenflcllmethylamme' melted at this period The mixture then suspended in 70 Recrystallization from ether gave purer material water-ether and shaken out with dilute hydromeltmg at 1695-17150 v ch'lo'ric acid. The aqueous layer containing sus- EXAMPLE II pended insoluble hydrochloride was separated A and madealkaline with dilute sodium carbonate 3'acetomy'5'temorchqZenyldzmethyzamme solution. The alkaline suspension was extracted .75 'A mixture of 3.59 g. of -3-acetoxy-5-ternorch01 enylamine, 8.57 g. of 90% formic acid and 35% aqueous formaldehyde solution was heated on the steam bath under reflux for four hours. The mixture was then-chilled, made basic with dilute sodium carbonate solution and extracted with ether. The ether extract was washed with water several times and-dried. The white crystalline residue remaining after removal of solvent was recrystallized from ether-petroleum ether. There resulted 2.1' g., first'crop, of crude 3-acetoxy-5- ternorcholenyldimethylamine. More of the amine may be obtained by concentration of the mother-liquor. The amine when purified by further recrystallization melts at 1845-1875 C.
EXAMPLE III 3-aeetozcyr-5-ternorcholenyldimethylamine A mixture of 20.5 g. of 3-acetoxy-5-ternorcholenylamine acetate, 17.85 g. of 90% formic acid and 35% aqueous formaldehyde was heated on a steam bath for five hours. Carbon dioxide was liberated at the beginning of the heating period. The mixture was diluted with water. After the addition of ether and dilute hydrochloric acid, the mixture was shaken and the aqueous layer containing suspended insoluble hydrochloride was separated. The aqueous suspension was made alkaline with dilute sodium carbonate solution and extracted with ether. The extract was washed with water and dried. Upon removal of solvent, there remained 17.8 g. of crude 3-acetoxy-5-ternorcholenyldimethylamine, M. P. 153- 175 C. Recrystallization from ether gave pure material melting at 184.5-187.5 C.
EXAMPLE IV 3-hydromy-5-androstene-17-dimethylamine 25 g. of 3-hydroxy-5-androstene-1'7-amine was added with cooling and shaking to 24 cc. of 90% formic acid. The slurry became brown. Then 1'7 cc. of 35-38% aqueous formaldehyde was added and the mixture was heated for four hours under reflux on the steam cone. The solid dissolved with copious evolution of C02. The solution was concentrated in vacuo to a thick sirup which was taken up in a mixture of ether and 5% aqueous hydrochloric acid. The acidic layer was made basic with sodium hydroxide and the amine extracted with ether. The ether solution was washed several times with water, dried and concentrated to about 150 cc. After chilling, the separated solid was filtered and washed with petroleum ether. Another crop was obtained from the mother-liquor. There resulted 19.0 g. of white crystalline 3-hydroxy-5-androstene-17- dimethylamine, M. P. 208-2l3 C.
EXAMPLE V 3-acetoa:y-allo-ternorcholanyZdimethylamine 1 4.2 g. of 3-acetoxy-allo-ternorcholanylamine acetate was mixed with 3 g. of 90% formic acid and 2 g. of 35% aqueous formaldehyde solution and heated on a steam bath for four hours. The solution was then concentrated in vacuo, diluted with 5% hydrochloric acid and extracted with ether. The acidic aqueous layer was made alkaline with 10% sodium hydroxide solution and extracted with ether. The ether extract was washed with water and dried. The residue remaining after removal of solvent was crystallized from benzene. The crude 3-acetoxy-allo-ternorcholanyldimethylamine melted at 147-153 C.
EXAMPLE VI 3 (a) ,12 (a) -diaoetoa:y-terncrcholanyldimethylamine The acid chloride was prepared from 7.2 g.v of 3(a) 12(a) -diacetoxy-bisnor-cholanic acid and 4.2 cc. of thionyl chloride in 20 cc. of dry benzene- 40 cc. of dry ether. After one hour the solvent .was removed and the acid chloride was dissolved in 130 cc. of acetone. This solution was treated, dropwise, at 0-5 C. with a solution of 2.3 g. of sodium azide in 10 cc. of water. The mixture was stirred for twenty minutes and the azide precipitated by the addition of 200 cc. of cold water. The solid azide was separated, suspended in 130 cc. of aqueous acetic acid and decomposed by heating to 50'-60 C. for one hour. The clear solution was steam distilled, neutralized with dilute sodium carbonate solution and extracted with ether. The washed and dried ether solution gave upon concentration 6.2 g. of crude 3(a), 12m) -diacetoxy ternorcholanylamine mide derivative, M. P. 220-221" 0.).
The crude amine was methylated by heating 5.2 gpin 6 cc. of formic acid and 4 cc. of 35% aqueous formaldehyde on the steam bath under reflux for four hours. The orange liquid Was poured into cold dilute sodium hydroxide and extracted with ether. The ether solution was washed with water, dried and concentrated in vacuo. The resulting amorphous material (5.5 g.) was crystallized from petroleum ether (B. P. 35-60 C.) yielding small needles of 3(a), 12(a) diacetoxy-ternorcholanyldimethylamine melting at 134-137 C.
Treatment of the ternorcholanyldimethylamine with methyl iodide in boiling benzene un-- der reflux gave the ether insoluble, solid quaternary methiodide.
EXAMPLE VII A solution of 3.6 g. of 3-keto-5-androstene-l7- amine acetate in 3.6 g. of formic acid and 2.6 g. of 35% aqueous formaldehyde was heated on the steam bath under reflux for four hours. Carbon dioxide was liberated. The liquid was diluted with sodium carbonate solution and extracted with benzene-chloroform. The extract was washed with water followed by dilute hydrochloric acid. The acidic extract was made alkaline with sodium carbonate solution and extracted with benzene-chloroform. The extract was then washed with water and dried. Concentration gave the crude 3-keto 5 androstenel -dimethylamine. This material can be crystallized from ether-petroleum ether (B. P. 35-60 C.) after treatment with activated alumina.
The crude amine gave an ether insoluble quaternary iodide when treated With methyl iodide in boiling benzene. It is soluble in water.
EXAIWPLE VIII 3-hydrory- 5-temorchoZenyZtrimethg Zammonium iodide (aceta- 7 EXAMPLE Ix 3ahydrory-5-etiocholenyZtrimethylammonium iodide A solution of 3.2g. of '3-hydroxy-5-androstenel'l-amine in 90 cc. of dry benzene was treated with 15 cc. of methyl iodide. The mixture was refiuxed until it was thick with crystalline solid material. washed with anhydrous ether. The product, B-hydroxy etiocholenyltrimethylammonium iodide, weighed 4.0 g. Recrystallization from methanol gave 3.5 g. of pale yellow needles.
EXAMPLE 2 3 -acetory-allo-temo1'ch0Zanyltrimethylammonium bromide .A solution of 0.5g. of S-acetoxy-allo-ternorcholanyldimethyla-mine in cc. of benzene was mixed with a solution of 5 g. of methyl bromide in 5 cc. of benzene. Themixture was refluxed for five hours. As heating-progressed the solution became cloudy and then a solid separated. After dilution with ether, the white solid was separated and washed well with ether. The product, 3 acetoxy allo ternorcholanyltrimethyl ammonium bromide, weighed 0.4.- g. The material is quite soluble in methanol but may be recrystallized from a cold, concentrated solution.
EXAMPLE XII 3-acetoscy-5-temorcholenyldimethylbeneylammonium chloride A solution of 1.0 .g. of 3 acetoxy 5 ternorcholenyldimethylamine in.10 cc. of benzylchloride was refluxed for minutes. The chilled mixture was diluted with ether and the white solid was filtered. This material, 0.4 g., was quite soluble in methanol but almost insoluble in ether. It is recrystallized from ether-methanol.
The fine crystals of 3-acetoxy-5-ternorcholenyldimethylbenzylammonium chloride decomposed slightly when heated to 285 C. but did .not melt. They proved to be partially soluble in water; the aqueous solution forming a white precipitate upon the addition of silver nitrate solution.
EXAMPLE XIII 3m micry-5-eticcholenyldimethylisoamylammonium bromide A solution of 1.0 g. of 3-hydroxy-5-androstenel7-dimethylamine in 10 cc. of isoamyl bromide was refluxed for one hour. After chilling the mixture was diluted with ether and the solid was filtered. The crystalline solid, 0.5 g., was poorly soluble in ether and slightly soluble in water. It may be recrystallized from methanol. This material, 3 hydroxy 5 etiocholenyldimethyl isoaznylammonium bromide does not meet below 250 C.
After chilling, the solid was filtered and a EXAMPLE EV 3 (a) ,12 (a) -diaceto.'z:y-bisnorch'olanyldimethylamine I "The acid chloride was prepared from 9.2 gfoi treated at 10 C. with a solution of 2.8 g. sodium.
azide .12 cc. Water, added dropwise in 10 minutes. The azidewas precipitated with 300cc. cold water as a gum, which was extracted with alcohol-free ether. The ethereal solution was washed, dried, concentrated in vacuo. The residual solid was dissolved in 160 cc. acetic acid and decomposed byheating one hour :at 15Dil0 .F. Thesolution was steam distilled, made alkaline with vsodiumcarbonate, extracted with ether, and theethereal solution ashaken out with.10% hydrochloric acid. The acid washes were made alkaline with sodium carbonate solution,.the amine extracted with ether, washed, and dried. On concentration 8.0 "g. amine was obtained (acetamide derivative M. .P. 215 0.).
Thecrude amine was methylated by heating 8.0 g, .in.8 cc. formic'acid'and 6 00. 38% aqueous formaldehyde'ior- 4 hours under reflux on the steambath. Thesolution was diluted with water. and 5 hydrochloric acid, shaken out with ether, and the water layer madealkaline with 5% sodium hydroxide. The white precipitate was extracted with ether, washed, dried, concentrated and crystallized from ether-petroleum ether (B. P. 35-60 C.). A total of 5.7 g. amine was obtained. On recrystallization from ether it melted at 108-171" C.
A 2.6 g. sample of the dimethylamine was dissclvedinSO cc. of benzene and treated with 5 cc. of methyliodide. After refluxing for one-half hour, the -quaternary -halide, 3(a),- 1'20)- diaoetoxy bisnorcholanyltrimethylammoniu-m iodide, was precipitated by the addition of ether.
-, The-mixture was chilled,filtered and the solid washed with ether. The crude quaternary 1ammoniu-m iodide weighed 3. 4 g.
EXAMPLE EJI 301) .12 0) -diucetorymorchoianylzfimethyiamine :The *diacetoxyderivative from 20:0. g'. of desoxych-oiic acid was converted to the acid chloride with 13 cc. of thionyl chloride-in cc. of .dry benezene-ZOO cc. of dry -ether,and one :drop 10% pyridine in benzene. After one and onehalf hours the solvent was removed in vacuo and the crystalline acid chlorideidissolved in 400 cc. of distilled acetone. This solution was cooled to 5 C. and a solution containing 7.0 g. or sodium azide in 30 cc. of distilled water was added during 30 minutes. The reaction was stirred for 30 minutes, then diluted with 600 cc. of cold water, added during one hour. Theprecipitated azide was filtered and washed with water. The moist aside was decomposed in 400 cc. 80% acetic acid at 70 C. for one hour, then steam distilled for 45 minutes. The reaction was made slightly alkaline with sodium carbonate and extracted with ether. The ethereal extract was washed, shaken out with 10% hydrochloric acid; the acid washes were "made alkaline with sodiumcar'oonate, extracted with ether, washed, dried, and concentrated. 15.7 g. of amine portion was obtained,
9 This crystallized from ether-petroleum-ether (B. P. 35-60 C.) as needles, M. P. 156-158 C.
20 g. of the crude amine was methylated in 20 cc. of 90% formic acid and 15 cc. of 38% aqueous formaldehyde by warming on the steam bath, under reflux, for sixteen hours. The reaction was diluted with water, poured with stirring into sodium carbonate solution and the amorphous solid filtered and washed. It was taken up in ether, the amine shaken out with 10% hydrochloric acid, and the acid washes made alkaline with sodium carbonate. The amine was extracted with ether, washed, dried, and concentrated. The residue Weighed 15.5 g. This material was dissolved in 100 cc. of methanol, 50 g. of methyl iodide added, and the solution refluxed for two hours. It was then concentrated, dry ether added, and 12.3 g. of methiodide was obtained as yellow crystals. On recrystallization this melted at 218-220 C.
The foregoing examples are illustrative of the invention, it being understood that various changes and modifications may be made therein without departing from the spirit and the scope of the invention. Thus, other alkyl and aralkyl iodides, bromides and chlorides may be used for the preparation of the quaternary halides.
10 Reference is made herein to the copending application of two of us, Serial No. 770,336, filed August 23, 1947. 7
Having described the invention, what is claimed is: l. Pregnene compounds selected from the class consisting of 20-dimethy1amino-5-pregnenes and their quaternary ammonium halides other than quaternary ammonium fluorides.
2. The quaternary ammonium halide compounds of claim 1.
3.v The trimethyl ammonium halides of claim 2. 4. 20-dimethylamino-5-pregnenes. 5. 3-acetoxy-20-dimethylamino-5-pregnene.
PERCY L. JULIAN. HELEN C. PRINTY. EDWIN W. MEYER.
REFERENCES CITED The following references are of record in the file of this patent:
UNITED STATES PATENTS Number Name Date 2,252,863 Raymond et al Aug. 19, 1941 2,481,524 MacPhillamy Sept. 13, 1949
Claims (1)
1. PREGNENE COMPOUNDS SELECTED FROM THE CLASS CONSISTING OF 2-DIMETHYLAMINO-5-PREGNENES AND THEIR QUATERNARY AMMONIUM HALIDES OTHER THAN QUATERNARY AMMONIUM FLUORIDES.
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Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3009925A (en) * | 1959-12-07 | 1961-11-21 | Upjohn Co | 17-aminoandrostanes |
US3107254A (en) * | 1960-10-05 | 1963-10-15 | Upjohn Co | 17beta-dialkylamino-17-cyanosteroids and their 17alpha-alkyl, alkylene and alkyne derivatives |
US3155690A (en) * | 1962-08-17 | 1964-11-03 | Abbott Lab | Nu-substituted 17alpha-aminosteroids |
US3189597A (en) * | 1959-03-04 | 1965-06-15 | Ciba Geigy Corp | 3-glycosides of 17-amino-3-hydroxy-5-androstenes |
US3257384A (en) * | 1963-01-04 | 1966-06-21 | Upjohn Co | Derivatives of 25-azacholesterol and 22-oxa-25-azacholesterol |
US20030083231A1 (en) * | 1998-11-24 | 2003-05-01 | Ahlem Clarence N. | Blood cell deficiency treatment method |
US20070203107A1 (en) * | 2002-08-28 | 2007-08-30 | Hollis-Eden Pharmaceuticals, Inc. | Pharmaceutical compositions |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2252863A (en) * | 1941-02-03 | 1941-08-19 | Searle & Co | Quaternary ammonium salts |
US2481524A (en) * | 1946-09-09 | 1949-09-13 | Ciba Pharm Prod Inc | Quaternary ammonium steroids and process |
-
1947
- 1947-09-11 US US773526A patent/US2561378A/en not_active Expired - Lifetime
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2252863A (en) * | 1941-02-03 | 1941-08-19 | Searle & Co | Quaternary ammonium salts |
US2481524A (en) * | 1946-09-09 | 1949-09-13 | Ciba Pharm Prod Inc | Quaternary ammonium steroids and process |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3189597A (en) * | 1959-03-04 | 1965-06-15 | Ciba Geigy Corp | 3-glycosides of 17-amino-3-hydroxy-5-androstenes |
US3009925A (en) * | 1959-12-07 | 1961-11-21 | Upjohn Co | 17-aminoandrostanes |
US3107254A (en) * | 1960-10-05 | 1963-10-15 | Upjohn Co | 17beta-dialkylamino-17-cyanosteroids and their 17alpha-alkyl, alkylene and alkyne derivatives |
US3155690A (en) * | 1962-08-17 | 1964-11-03 | Abbott Lab | Nu-substituted 17alpha-aminosteroids |
US3257384A (en) * | 1963-01-04 | 1966-06-21 | Upjohn Co | Derivatives of 25-azacholesterol and 22-oxa-25-azacholesterol |
US20030083231A1 (en) * | 1998-11-24 | 2003-05-01 | Ahlem Clarence N. | Blood cell deficiency treatment method |
US20070203107A1 (en) * | 2002-08-28 | 2007-08-30 | Hollis-Eden Pharmaceuticals, Inc. | Pharmaceutical compositions |
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