Novel 19-nor steroids of the formula ##STR1## wherein R' is selected from the group consisting of propyl, propenyl, iodoethenyl, iodoethynyl or --C.tbd.C--CH.sub.2 --Hal.sub.1, Hal.sub.1 is selected from the group consisting of fluorine, chlorine and bromine and their non-toxic, pharmaceutically acceptable acid addition salts having a remarkable antiglucocorticoid and antiprogestomimetic activity.

STATE OF THE ART 
Relevant prior art includes U.S. Pat. Nos. 4,233,296; 4,447,424; 4,519,946 
and 4,634,695. 
OBJECTS OF THE INVENTION 
It is an object of the invention to provide the novel compounds of formula 
I and their non-toxic, pharmaceutically acceptable acid addition salts and 
a process for their preparation. 
It is another object of the invention to provide antiglucocorticoid and 
antiprogestomimetic compositions and a method of inducing 
antiglucocorticoidal and antiprogestomimetic activity in warm-blooded 
animals. 
These and other objects and advantages of the invention will become obvious 
from the following detailed description. 
THE INVENTION 
The novel compounds of the invention are selected from the group consisting 
of 19-nor steroids of the formula 
##STR2## 
wherein R' is selected from the group consisting of propyl, propenyl, 
iodoethenyl, iodoethynyl or --C.tbd.C--CH.sub.2 --Hal.sub.1, Hal.sub.1 is 
selected from the group consisting of fluorine, chlorine and bromine and 
their non-toxic, pharmaceutically acceptable acid addition salts. 
Preferably, when R' is iodoethenyl, the double bond has E or Z geometry and 
when R' is propenyl, the double bond has Z geometry. 
Specific preferred compounds of the invention are 
17.alpha.-(3-chloro-1-propynyl)-11.beta.-[4-(dimethylamino)-phenyl]-.DELTA 
..sup.4,9 -estradien-17.beta.-ol-3-one, 
11.beta.-[4-(dimethylamino)-phenyl]-17.alpha.-(3-fluoro-1-propynyl)-.DELTA 
..sup.4,9 -estradien-17.beta.-ol-3-one, 
11.beta.-[4-(dimethylamino)-phenyl]-21-iodo-19-nor-17.alpha.-.DELTA..sup.4 
,9 -pregnadien-20-yn-17.beta.-ol-3-one, (E) 
11.beta.-[4-(dimethylamino)-phenyl]-21-iodo-19-nor-17.alpha.-.DELTA..sup.4 
,9,20 -pregnatrien-17.beta.-ol-3-one, (Z) 
11.beta.-[4-(dimethylamino)-phenyl]-21-iodo-19-nor-17.alpha.-.DELTA..sup.4 
,9,20 -pregnatrien-17.beta.-ol-3-one, 
11.beta.-[4-(dimethylamino)-phenyl]-17.alpha.-[(Z)-1-propenyl)-.DELTA..sup 
.4,9 -estradien-17.beta.-ol-3-one, 
11.beta.-[4-(dimethylamino)phenyl)]-17.alpha.-propyl-.DELTA..sup.4,9 
-estradien-17.beta.-ol-3-one and 
17.alpha.-(3-bromo-1-propynyl)-11.beta.-[4-(dimethylamino)-phenyl]-.DELTA. 
.sup.4,9 -estradien-17.beta.-ol-3-one and their non-toxic, pharmaceutically 
acceptable acid addition salts. 
Among the especially preferred compounds of the invention are in 
particular: 11.beta.-[4-(dimethylamino)-phenyl]-17.alpha.-(3-fluoro-1-prop 
ynyl)-.DELTA..sup.4,9 -estradien-17.beta.-ol-3-one, (Z) 
11.beta.-[4-(dimethylamino)-phenyl]-21-iodo-19-nor-17.alpha.-.DELTA..sup.4 
,9,20 -pregnatrien-17.beta.-ol-3-one and 
11.beta.-[4-(dimethylamino)-phenyl]-17.alpha.-[(Z)-1-propenyl]-.DELTA..sup 
.4,9 -estradien-17.beta.-ol-3-one and their non-toxic, pharmaceutically 
acceptable acid addition salts. 
The process of the invention for the preparation of a compound of the 
formula 
##STR3## 
wherein Hal.sub.1 has the above definition comprises reacting a compound 
of the formula 
##STR4## 
with a bromination or chlorination agent such as triphenylphosphine 
reacted with carbon tetrabromide or carbon tetrachloride in the presence 
of a solvent such as tetrahydrofuran or methylene chloride to obtain the 
compound of formula I.sub.2A wherein Hal.sub.1 is chlorine or bromine and 
optionally reacting the latter with a fluorine exchange agent such as 
cesium fluoride or potassium fluoride in the presence of 18 crown 6 ether 
in acetonitrile. 
The process for the preparation of compounds of the formula 
##STR5## 
wherein the double bond has E or Z geometry comprises reacting a compound 
of the formula 
##STR6## 
wherein k is a protected ketone such as ethylenedioxy with a reducing 
agent such as tributyltin hydride in the presence of azoisobutyronitrile 
to obtain an E bond or in a polar aprotic solvent such as 
hexamethylphosphotriamide to obtain a Z bond, reacting the latter with an 
iodization agent such as N-iodosuccinimide and then with a hydrolyzing 
agent to obtain the compound of formula I.sub.2B with the double bond 
having E or Z geometry. 
The process of the invention for the preparation of a compound of the 
formula 
##STR7## 
comprises reacting a compound of the formula 
##STR8## 
with an iodization agent such as N-iodo-succinimide in the presence of a 
silver salt such as silver carbonate or silver nitrate to obtain a 
compound of formula I.sub.2C. 
The process of the invention for the preparation of a compound of the 
formula 
##STR9## 
wherein the dotted line is a single or double bond Z comprises reacting a 
compound of the formula 
##STR10## 
with hydrogen in the presence of a catalyst such as palladized barium 
sulfate poisoned with an amine such as pyridine or triethylamine to obtain 
a mixture of predominately a compound of the formula I.sub.2D wherein the 
dotted line is a second bond and Z geometry and a minor amount wherein the 
dotted line is a single bond. 
Compound P.sub.1 is described in French Pat. No. 2,566,779 and compounds 
P.sub.2 and P.sub.3 are described in European Pat. No. 0,057,115. Compound 
P.sub.4 is described in French Pat. No. 2,497,807. The compounds of 
formula I fall within the scope of the broad formula of European Pat. No. 
0,057,115 but are not described therein. 
Examples of suitable salts for the preparation of the non-toxic, 
pharmaceutically acceptable acid addition salts are inorganic acids such 
as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid and 
nitric acid and organic acids such as formic acid, acetic acid, propionic 
acid, fumaric acid, maleic acid, benzoic acid, aspartic acid, glycolic 
acid, succinic acid, alkane sulfonic acids such as methane sulfonic acid, 
ethane sulfonic acid and aryl sulfonic acids such as benzene sulfonic 
acid. 
The novel antiglucocorticoid and antiprogestomimetic compositions of the 
invention are comprised of an effective amount of at least one compound of 
formula I and their non-toxic, pharmaceutically acceptable acid addition 
salts and an inert pharmaceutical carrier or excipient. The compositions 
may be in the form of tablets, dragees, gelules, granules, suppositories, 
ointments, creams, gels and injectable solutions or suspensions. 
Examples of suitable excipients are talc, arabic gum, lactose, starch, 
magnesium stearate, cocoa butter, aqueous and non-aqueous vehicles, fatty 
substances of animal or vegetable origin, paraffinic derivatives, glycols, 
various wetting agents, surfactants and emulsifiers and preservatives. 
In addition to their antiglucocorticoid and antiprogestomimetic activity, 
the compositions also possess androgen or antiandrogenic properties. 
Because of their antiglucocorticoid activity, the compositions are useful 
to counteract the side effects of glucocorticoids and are also useful to 
treat conditions caused by hypersecretion of glucocorticoid and especially 
against ageing in general and more particularly against hypertension, 
atherosclerosis, osteoporosis, diabetes, obesity as well as depression of 
immunity and insomnia. The compositions due to their antiprogestomimetic 
properties are useful as original contraceptives. They can also be used 
against hormonal disturbances and, furthermore they may present an 
interest in the treatment of hormone-dependent cancers. 
The compositions possess antiprogestomimetic properties and can also be 
used in veterinary medicine as abortifacients and have particular use with 
female cats and dogs. The preferred veterinary medicaments contain 
11.beta.-[4-dimethylaminophenyl]-17.alpha.-[(Z)-1-propenyl]-.DELTA..sup.4, 
9 -estradien-17.beta.-ol-3-one. 
The novel method of the invention for inducing antiglucocorticoid and 
antiprogestomimetic activity in warm-blooded animals, including humans, 
comprises administering to warm-blooded animals an effective amount of at 
least one compound of Formula I and their non-toxic, pharmaceutically 
acceptable acid addition salts. The usual daily dosage is 0.13 to 13.33 
mg/kg depending on the method of administration, the specific compound and 
the condition being treated. The compounds may be administered orally, 
rectally, parenterally or topically. 
When used as abortifacients for female cats and dogs, the compounds may be 
administered with 1 to 3 injections per day at 3 to 5 mg/kg. For example, 
the compound of Product A of Example 6 may be administered at 5 mg/kg 
injections at 24 hour intervals for a female dog. For this use, the 
preferred compound is 
11.beta.-(4-dimethylamino-phenyl)-17.alpha.-[(.DELTA.Z)-1-propenyl]-.DELTA 
..sup.4,9 -estradiene-17.beta.-ol-3-one. 
When the active compound to be administered is an antiglucocorticoid or an 
antiprogestomimetic, the preferred compounds are the compounds of Examples 
2, 5 and 6 (Product A) and the usual oral dosages is 1.33 to 13.3 mg/kg. 
In the following examples there are described several preferred embodiments 
to illustrate the invention. However, it should be understood that the 
invention is not intended to be limited to the specific embodiments.

EXAMPLE 1 
17.alpha.-(3-chloro-1-propynyl)-11.beta./4-(dimethylamino)-phenyl.DELTA..su 
p.4,9 -estradiene-17.beta.-ol-3-one 
800 mg of 
11.beta.-[4-(dimethylamino)-phenyl]-17.alpha.-(3-hydroxy-1-propynyl)-.DELT 
A..sup.4,9 -estradiene-17.beta.-ol-3-one described in French Pat. No. 
2,566,779 were dissolved in 8 ml of tetrahydrofuran and 8 ml of carbon 
tetrachloride and 950 mg of triphenylphosphine were added. The mixture was 
stirred at 90.degree. C for 3 hours and a slightly insoluble product was 
filtered off. The filtrate was evaporated to dryness to obtain 1.40 g of 
crude product which was purified by chromatography on a silica column. 
Elution with a mixture of petroleum ether (b.p.: 40.degree.-70.degree. C.) 
and ethyl acetate (50/50) yielded 420 mg of pure expected product in the 
form of a crystalline solid melting at 238.degree. C. 
IR Spectrum (CHCl.sub.3): OH 3600 cm.sup.-1 ; C.dbd.O conjugated : 1655 
cm.sup.-1 ; C.dbd.C conjugated and aromatic; 1612/1562/1518 cm.sup.-1. 
EXAMPLE 2 
11.beta.-[4-(dimethylamino)-phenyl]-17.alpha.-(3-fluoro-1-propynyl)-.DELTA. 
.sup.4,9 -estradien-17.beta.-ol -3-one 
313 mg of 
17.alpha.-(3-chloro-1-propynyl)-11.beta.-[4-(dimethylamino)-phenyl]-.DELTA 
..sup.4,9 -estradien-17.beta.-ol-3-one were added with stirring to 10 mg of 
dry acetonitrile containing 600 ml of potassium fluoride and 600 mg of 
18-crown 6 ether heated to 90.degree. C. under an inert atmosphere. After 
23 hours at reflux, the solvent was evaporated and the residue was 
dissolved in water and extracted by ethyl acetate. After washing with 
salted water and drying over magnesium sulfate, the organic phase was 
evaporated to dryness to obtain 322 mg of crude product which was purified 
by chromatography on silica column. Elution with a mixture of methylene 
chloride/ethyl acetate 90/10 yielded 79 mg of pure expected product which 
was crystallized from a mixture of methylene chloride and isopropyl ether 
to obtain 55 mg of the expected product melting at 234.degree.-235.degree. 
C. 
IR Spectrum (CHCl.sub.3): OH 3600 cm.sup.-1 ; C.dbd.O conjugated: 1655 
cm.sup.-1 ; C.dbd.C conjugated+aromatic; 1612/1562/1568 cm.sup.-1, 
EXAMPLE 3 
11.beta.-[4-(dimethylamino)-phenyl]-21-iodo-19-nor-17.alpha.-.DELTA..sup.4, 
9 -pregnadien-20-yn-17.beta.-ol-3-one 
975 mg of 
11.beta.-[4-(dimethylamino)-phenyl]-19-nor-17.alpha.-.DELTA..sup.4,9 
-pregnadien-20-ol-3-one were dissolved in 20 ml of acetone and 640 mg of 
silver carbonate then 450 mg of N-iodosuccinimide were added. The mixture 
was stirred for 4 hours and then was poured into a 10% aqueous solution of 
sodium thiosulfate and extracted with methylene chloride. The organic 
phase was washed with water, dried and evaporated to dryness to obtain 1.2 
g of crude product which was chromatographed on silica. Elution at first 
with a cyclohexane-ethyl acetate mixture (6-4) yielded 390 mg of expected 
product and 760 mg of a mixture which was chromatographed on silica and 
eluted with a hexane-ether mixture (3-7) to obtain 530 mg of expected 
product. 920 mg of the product obtained were crystallized from ether to 
obtain 730 mg of product melting at 210.degree. C. Another 79 mg of 
additional product was obtained from the mother liquors. 
IR Spectrum (CHCl.sub.3): OH 3598 cm.sup.-1 ; C.dbd.C 2174 cm.sup.-1 ; 
Dienone 1654 cm.sup.-1 ; Aromatic 1612/1562/1518 cm.sup.-1. 
EXAMPLE 4 
(E) 
11.beta.-[4-(dimethylamino)-phenyl]-21-iodo-19-nor-17.alpha.-.DELTA..sup.4 
,9,20 -pregnatrien-17.beta.-ol-3-one 
Step A: (E) (1,2-ethanediyl) cyclic acetal of 
11.beta.-[4-(dimethylamino)-phenyl]-21-iodo-19-nor-17.alpha.-.DELTA..sup.9 
,20 -pregnadien-5.alpha., 17.beta.-diol-3-one 
(1) 1.5 g of (1,2-ethanediyl) cyclic acetal of 
11.beta.-[4-(dimethylamino)-phenyl]-19-nor-17.alpha.-.DELTA..sup.9 
-pregnen-20-yn-5.alpha., 17.beta.-diol-3-one were dissolved in 30 ml of 
anhydrous tetrahydrofuran and 8 ml of tributyltin hydride and 300 mg of 
azoisobutyronitrile were added. The mixture was refluxed for 50 minutes 
and after concentrating under reduced pressure, the residual oil was 
diluted with methylene chloride and chromatographed on silica. Elution 
with a cyclohexane-ethyl acetate mixture (7-3) yielded 2.96 g of 
intermediary tributylstannylvinyl derivative. 
(2) The latter was dissolved in 30 ml of anhydrous tetrahydrofuran, and 900 
mg of N-iodosuccinimide were added. After 25 minutes of reaction, the 
mixture was poured into a 10% aqueous solution of sodium thiosulfate and 
extracted with methylene chloride. The organic phase was washed with 
water, dried and evaporated to dryness. The residue was taken into with 
isopropyl ether at reflux, then cooled with ice and separated to obtain 
1.66 g of the expected product melting at 246.degree. C. 
IR Spectrum (CHCl.sub.3): Free OH: 3600 cm.sup.-1 ; OH in 5: 3500 cm.sup.-1 
; Aromatics: 1613/1517 cm.sup.-1. 
Step B: (E) 
11.beta.-[4-(dimethylamino)-phenyl]-21-iodo-19-nor-17.alpha.-.DELTA..sup.4 
,9,20 -pregnatrien-17.beta.-ol-3-one 
1.66 g of the product of Step A were dissolved in 16 ml of methanol and 16 
ml of 2N hydrochloric acid and the solution was stirred for 1 hour at 
ambient temperature. The mixture was poured into an aqueous solution of 
sodium bicarbonate, filtered and the precipitate was re-dissolved in 
methylene chloride. The organic phase was dried and evaporated to dryness 
under reduced pressure. The residue was chromatographed on silica and 
eluted with a cyclohexane-ethyl acetate mixture (7-3) to obtain 1.28 g of 
crude product. After dissolution in methylene chloride, concentration, 
then crystallization by the addition of ether, 1.125 g of the expected 
product melting at 236.degree. C. after crystallization from ethanol were 
obtained. 
IR Spectrum (CHCl.sub.3): dienone C.dbd.O: 1654 cm.sup.-1 ; C.dbd.C: 1612 
cm.sup.-1 ; Aromatic: 1518 cm.sup.-1 ; OH: 3600 cm.sup.-1. 
EXAMPLE 5 
(Z) 
11.beta.-[4-(dimethylamino)-phenyl]-21-iodo-19-nor-17.alpha.-.DELTA..sup.4 
,9,20 -pregnatrien-17.beta.-ol-3-one 
Step A: (Z) (1,2-ethanediyl) cyclic acetal of 
11.beta.[4-(dimethylamino)-phenyl]-21-tributylstannyl-19-nor-17.alpha.-.DE 
LTA..sup.9,20 -pregnadien-5.alpha.,17.beta.-diol-3-one 
477 mg of (1,2-ethanediyl) cyclic acetal of 
11.beta.-[4-(dimethylamino)-phenyl]-19-nor-17.alpha.-.DELTA..sup.9 
-pregnen-20-yn-5.alpha.,17.beta.-diol-3-one were dissolved in 5 ml of 
hexamethylphosphorotriamide and 2,6 ml of tributyltin hydride were added 
under an inert atmosphere. The mixture was heated to 70.degree. C. for 25 
hours, then cooled, diluted with water and extracted with ethyl acetate. 
The organic phase was washed with water, dried and concentrated to 
dryness. The residue was chromatographed on silica and eluted with a 
petroleum-ether (b.p: 40.degree.-70.degree. C.) /ether mixture (6-4) to 
obtain 214 g of isomer (E), 135 mg of the mixture of isomers (E) and (Z) 
and 346 mg of the expected isomer (Z). 
Step B: (Z) 
11.beta.-[4-(dimethylamino)-phenyl]-21-iodo-19-nor-17.alpha.-.DELTA..sup.4 
,9,20 -pregnatrien-17.beta.-ol-3-one 
1.47 g of the isomer (Z) of Step A were dissolved in 30 ml of 
tetrahydrofuran and 520 mg of N-iodosuccinimide were added with stirring. 
After 30 minutes at ambient temperature, the mixture was poured into an 
aqueous solution of sodium thiosulfate and extracted with ethyl line 
dropped to dryness. 10 ml of methanol and 10 ml of 2N hydrochloric acid 
were added to the residue which stood for 1 hour. The mixture was then 
alkalized with a solution of sodium bicarbonate and extracted with 
methylene chloride. The organic phase was washed with water, dried, then 
concentrated to dryness to obtain 1.36 g of crude product. The residue was 
chromatographed on silica and eluted with a cyclohexane-ethyl acetate 
mixture to obtain 600 mg of the expected product melting at 178.degree. C. 
after crystallization from ether. 
IR Spectrum (CHCl.sub.3): Region C.dbd.O: 1650 cm.sup.-1 ; C.dbd.C: 1612 
cm.sup.-1 ; Aromatic: 1518 cm.sup.-1 ; OH: 3590 cm.sup.-1 and 3540 
cm.sup.-1. 
EXAMPLE 6 
(Z) 
11.beta.-[4-(dimethylamino)-phenyl]-17.alpha.-[(Z)1-propenyl]-.DELTA..sup. 
4,9 -estradien-17.beta.-ol-3-one (Product A) and 
11.beta.-[4-(dimethylamino)-phenyl]-17.alpha.-propyl-.DELTA..sup.4,9 
-estradien-17.beta.-ol-3-one (Product B) 
1 g of 
11.beta.-[4-(dimethylamino)-phenyl]-17.alpha.-(1-propynyl)-.DELTA..sup.4,9 
-estradien-17.beta.-ol-3-one were dissolved in 50 ml of ethanol and 1 ml 
of triethylamine and 75 mg of 10% palladium hydroxide on barium sulfate 
were added. The mixture was hydrogenated at ordinary temperature and it 
was stopped after the absorption of 55 ml of hydrogen. The catalyst was 
filtered off, the product was rinsed in ethanol and then the solvents were 
evaporated to obtain 1.076 g of crude product which was chromatographed on 
a silica column (eluant cyclohexane-ethyl acetate; 70-30). The following 
were obtained in succession: 92 mg of (Z) 
11.beta.-[4-(dimethylamino)-phenyl]-17.alpha.-[(Z)1-propenyl]-.DELTA..sup. 
5(10) -estren-17.beta.-ol-3-one (Rf: 0.40). 568 mg (Z) 
11.beta.-[4-(dimethylamino)-phenyl]-17.alpha.-[(Z)1-propenyl]-.DELTA..sup. 
4,9 -estradien-17.beta.-ol-3-one (Rf: 0.27 Product A) and 59 mg of 
11.beta.-[4-dimethylamino-phenyl]-17.alpha.-propyl-.DELTA..sup.4,9 
-estradien-17.beta.-ol-3-one (RF: 0.24) (Product B). 
PHYSICOCHEMICAL CONSTANTS OF PRODUCT A 
Analysis: C.sub.29 H.sub.37 NO.sub.2 ; molecular weight=431.63 Calculated: 
C % 80.70; H % 8.64; N % 3.25. Found: C % 80.34; H % 8.7; N % 3.2. 
IR Spectrum (CHCl.sub.3): OH at 3608 cm.sup.-1 ; C.dbd.O and C.dbd.C 
conjugated 1654/1612 cm.sup.-1 ; aromatic 1580/1518 cm.sup.-1. 
UV Spectrum (Et OH); Max 258 nm=17,900; Max 303 nm=22,700; +HCL 0.1N max; 
301 nm=21,300. 
PHYSIOCHEMICAL CONSTANTS OF PRODUCT B 
IR Spectrum (CHCl.sub.3) OH at 3615 cm.sup.-1 C.dbd.O/C.dbd.C conjugated 
1654/1612 cm.sup.-1 ; Aromatic 1560/1518 cm.sup.-1. 
EXAMPLE 7 
17.alpha.-(3-bromo1-propynyl)-11.beta.-[4-(dimethylamino)-phenyl]-.DELTA..s 
up.4,9 -estradien-17.beta.-ol-3-one 
600 mg of 
11.beta.-[4-(dimethylamino)-phenyl]-17.alpha.-(3-hydroxy-1-propynyl)-.DELT 
A..sup.4,9 -estradien-17.beta.-ol-3-one were dissolved in 6 ml of methylene 
chloride with 491 mg of carbon tetrabromide and after the solution was 
cooled to -10.degree. C., a solution of 531 mg of triphenylphosphine in 3 
ml of methylene chloride was added dropwise. The mixture was stirred for 
20 minutes at -10.degree. C. and was placed on a silica column of 15 g of 
silica and eluted with a mixture of petroleum-ether (b.p. 
40.degree.-70.degree. C.)/ethyl acetate 50/50 to obtain 384 g of pure 
expected product in solid crystalline form. 
PHARMACEUTICAL COMPOSITIONS 
Tablets were prepared containing 200 mg of the product of Example 6 
(Product A) and sufficient quantity of excipient of talc, starch, 
magnesium stearate for a tablet weight of 350 mg. 
VETERINARY COMPOSITIONS 
An injectable solution was prepared containing 100 mg of the product of 
Example 6 (Product A), 0.3 ml of ethanol and peanut oil q.s.p. to 3 ml. 
PHARMACOLOGICAL STUDY 
I. Study of the activity of the products of the invention on the hormonal 
receptors: 
A. Progesterone receptor in the uterus of a female rabbit: 
Impuberal rabbits of approximately 1 kg received a cutaneous application of 
25 g estradiol and 5 days after the treatment, the animals were killed. 
The uteruses were removed, weighed and homogenized at 0.degree. C. with 
the help of a Potter Teflon glass in a buffer solution (Tris 10 mM, 
saccharose 0.25M. 
HCl pH 7.4) (1 g of tissue for 50 ml of TS). The homogenate was then 
ultra-centrifuged (105,000 g.times.90 min) at 0.degree. C. The supernatant 
aliquotes thus obtained were incubated at 0.degree. C. for a time t, with 
a constant concentration (T) of Product R tritiated 
(17,21-dimethyl-19-nor-.DELTA.4,9-pregnadien-3,20-dione) in the presence 
of increasing concentrations (0-2,500. 10.sup.-9 M) either of cold R, or 
of cold progesterone, or of the cold product to be tested. The 
concentration of bound tritiated R (B) was then measured in each incubate 
by the absorption technique by dextran carbon. 
B. Glucocorticoid receptor in the thymus of a rat: 
Male Sprague-Dawley EOPS rats weighing 160 to 200 g underwent 
suprarenalectomies. 4 to 8 days after this removal, the animals were 
killed and the thymus were removed and homogenized at 0.degree. C. in Tris 
10 mM buffer, saccharose 0.25M, dithiothreitol 2 mM, HCl pH, 7, 4, in a 
Potter polytetrafluoroethylene-glass (1 g of tissue for 10 ml of TS). The 
homogenate was then ultra-centrifuged (105,000 g.times.90 mn) at 0.degree. 
C. Aliquotes of the supernatant thus obtained were incubated at 0.degree. 
C. for a time (t) with a constant concentration (T) of dexamethasone 
tritiated in the presence of increasing concentrations (0-2,500. 10.sup.9 
M) either of cold dexamethasone or of cold product to be tested. The 
concentration of bound tritiated dexamethasone (B) was then measured in 
each incubate by the technique of adsorption on carbon dextran. 
C. Calculation of the relative affinity of bonding: 
The calculation of the relative affinity of bonding (RAB) was indentical 
for all the receptors.. The following 2 curves were traced: the percentage 
of the tritiated hormone in B as a function of the logarithm of the 
concentration of the cold product tested. The straight line of the 
equation 
##EQU1## 
B max=Percentage of the tritiated bound hormone for an T incubation of 
this tritiated hormone at the concentration (T). 
B min=Percentage of the tritiated bound hormone for an T incubation of this 
tritiated hormone at the concentration (T), in the presence of a great 
excess of cold hormone (2500. 10.sup.-9 M). 
The intersections of the straight line I.sub.50 and the curves permit the 
evaluation of the concentrations of the reference cold hormone (CH) and of 
the cold product tested (CX) which inhibited by 50% of the bonding of the 
tritiated hormone on the receptor. 
The relative affinity of the bonding (RAB) of the product tested is 
determined by the equation: 
______________________________________ 
##STR11## 
The following results were obtained: 
Products of the examples 
Incubation Progestrogen Glucocorticoid 
time at 0.degree. C. 
2H 24H 4H 24H 
______________________________________ 
1 72 286 139 159 
5 41 184 146 113 
6 (Product A) 
96 491 147 115 
______________________________________ 
ABORTIVE ACTIVITY IN THE FEMALE DOG 
Preparation of the solution of the product to be studied 
250 mg of the product to be studied were dissolved in 1 ml of methylene 
chloride and then 1 ml of this solution was diluted with sesame oil until 
250 ml of the final solution was obtained. 
The state of gestation of the from 16 months to 4 years old female dogs, is 
determined by echography and the duration of the gestation is noted which 
extends from 25 to 40 days. 
The product to be studied is administered sub-cutaneously in solution 
corresponding to the preparation above in a 5 mg/kg dose and 2 injections 
are given at an interval of 24 hours. 
A control echograph is carried out 3 to 10 days after the last injection. 
3 days after the injection of the product of example 6 (Product A) an 
abortion was observed in 66% of the cases. 
10 days after the injection of the product of example 6 (Product A) a 
complete abortion was observed in all the animals in the group. 
ABORTIVE ACTIVITY IN THE FEMALE RABBIT 
10 days after covering the female rabbits received a sub-cutaneous 
injection of the product to be studied in a solution corresponding to the 
preparation above, in a 4 mg/kg and 5 mg/kg dosage was effected and 10 
days after the treatment, the animals were killed and the number of 
abortions which has taken place were noted at the autopsy. A complete 
abortion had taken place in all of the animals of the group with the 
product of Example 6 (Product A) administered in 4 mg/kg and 5 mg/kg 
dosage. 
Various modifications of the products and method may be made without 
departing from the spirit of scope thereof and it is to be understood that 
the invention is intended to be limited only as defined in the appended 
claims.