302-22-7 Usage
Description
Chlormadinone acetate is a synthetic progestin. It binds to progesterone, androgen, and glucocorticoid receptors in vitro (Kis = 2.5, 3.8, and 16 nM, respectively, for the human receptors). Chlormadinone acetate increases the number of endometrial glands and uterine weight in β-estradiol-primed rabbits when administered at a dose of 45 μg/kg per day for five days. Chlormadinone acetate reduces testosterone-induced increases in the seminal vesicle weight of castrated male rats when administered at doses of 4.6 and 21.5 mg/kg per day for eight days.
Chemical Properties
Crystalline Solid
Originator
Chlormadinone,Teikoku Hormone Mfg
Uses
Different sources of media describe the Uses of 302-22-7 differently. You can refer to the following data:
1. Orally active progesteron with antiandrogenic activity; has been used in combinations as an oral contraceptive.
Progestogen; antineoplastic (hormonal)
2. tranquilizer, neuroleptic, alpha adrenergic blocker
3. Orally active progesteron with antiandrogenic activity; has been used in combinations as an oral contraceptive. Progestogen; antineoplastic (hormonal).
Manufacturing Process
10 g 6-dehydro-17α-acetoxy-progesterone was dissolved in 400 ml dioxane
and 40 ml water. The solution was added to 4 g N-chlorosuccinimide and 2.4
ml 70% perchloric acid. The mixture was left at ambient temperature for 24
hours, whereupon it was poured in water, a dropping precipitate was filtered
off, washed with water and dried. It was filtered through aluminum oxide and
recrystallized from ether to give 6-chloro-6-dehydro-17α-acetoxyprogesterone (chlormadinone acetate). MP: 204°-206°C. [α]D= +54.6°
(chloroform).
Brand name
Gestafortin;Luteran;Ovosiston.
Therapeutic Function
Progestin
World Health Organization (WHO)
Chlormadinone acetate, a synthetic progestogen, was introduced
in 1965 as a component in oral contraceptive preparations. In 1967, as a result of
new regulations required by the United States Food and Drug Administration,
chlormadinone acetate was submitted to long-term toxicity studies and by the early
1970s it was shown to be associated with an increased incidence of mammary
tumours in beagle bitches which led to its withdrawal by several regulatory
authorities. Subsequently the validity of the beagle bitch model as a predictor of
carcinogenicity of steroid contraceptives has been contested by many national
regulatory authorities and chlormadinone remains available in some countries for
contraceptive purposes. In some instances it is indicated for treatment of
progesterone deficiency and endometriosis, and of irregular uterine bleeding due
to fibroids.
(Reference: (WHODI) WHO Drug Information, 84.1, 5, 1984)
Safety Profile
Suspected carcinogen
with experimental carcinogenic and
tumorigenic data. Moderately toxic by
intraperitoneal route. Human maternal and
reproductive effects by ingestion,
intramuscular, and possibly other routes:
ovary, uterus, cervix, vagina, and fallopian
tube changes; menstrual cycle changes or
disorders; changes in ferthty; and other
unspecified female effects. A human
teratogen that causes developmental
abnormalities of the endocrine system in the
fetus. Experimental teratogenic and
reproductive effects. An oral contraceptive.
When heated to decomposition it emits
toxic fumes of Cl-.
in vitro
when compared with other progesterone derivatives, chlormadinone showed a relatively strong positional effect. chlormadinone was found to have high binding affinity to the progesterone receptor, resulting in strong progestogenic activity at the endometrium level. chlormadinone could also prevent the lh surge in the same way as progesterone. in addition, chlormadinone could weakly bind to the glucocorticoid receptor, but not to either mineralocorticoid nor estrogen receptors. chlormadinone at high doses competed effectively with androgens to block their effects and also downregulated the number of androgen receptors [1].
in vivo
results from previous rat study showed that chlormadinone at low doses, similar to cyproterone acetate, was able to selectively impaire the epididymal function and maturation of spermatozoa without appreciably changing either testicular function or pituitary gonadotrophin secretion [2].
references
[1] bouchard p. chlormadinone acetate (cma) in oral contraception--a new opportunity. eur j contracept reprod health care. 2005;10 suppl 1:7-11.[2] sharma mm,lal g,jacob d. effects of low doses of chlormadinone acetate in the rat. j reprod fertil.1976 sep;48(1):177-9.
Check Digit Verification of cas no
The CAS Registry Mumber 302-22-7 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 3,0 and 2 respectively; the second part has 2 digits, 2 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 302-22:
(5*3)+(4*0)+(3*2)+(2*2)+(1*2)=27
27 % 10 = 7
So 302-22-7 is a valid CAS Registry Number.
InChI:InChI=1/C23H29ClO4/c1-13(25)23(28-14(2)26)10-7-18-16-12-20(24)19-11-15(27)5-8-21(19,3)17(16)6-9-22(18,23)4/h11-12,16-18H,5-10H2,1-4H3/t16?,17?,18?,21-,22+,23+/m1/s1
302-22-7Relevant articles and documents
Le Mathieu et al.
, p. 291,293 (1971)
Novel C-6 substituted and unsubstituted pregnane derivatives as 5α-reductase inhibitors and their effect on hamster flank organs diameter size
Cabeza, Marisa,Zambrano, Armando,Heuze, Ivonne,Carrizales, Erick,Palacios, Anay,Segura, Tania,Valencia, Norma,Bratoeff, Eugene
experimental part, p. 793 - 802 (2009/12/01)
The present study is addressed to ascertain the inhibitory effect of several progesterone derivatives having a chlorine substituent at C-6 (12a-12d), 15 with a bromine substituent at C-6 and 14a-14d, without any halogen atom at C-6 all having an ester side chain at C-17 (benzoate ester bearing a Cl, F and a Br atom at C-4 position of the phenyl ring) on the 5α-reductase enzyme activity present in human prostate. In addition, it was also of interest to investigate the pharmacological effect on hamster flank organs diameter size. In order to study the structure-activity relationships of steroids 12a-12d, 14a-14d and 15 we determined the concentration of these steroids that inhibited 50% of the activity of human prostate 5α-reductase enzyme (IC50), as well as the in vivo effect of these compounds in the hamster flank organs diameter size. We also ascertained, the capacity of these steroids to bind to the androgen receptors present in the rat prostate cytosol using labeled mibolerone (MIB) for monitoring the binding to the androgen receptor. The results from this study indicated that compounds 12a-12d (having a chlorine substituent at C-6), 14a-14d (lacking a halogen atom at C-6), 13 and 15 (having a bromine atom at C-6) showed an increased antiandrogenic effect (lower value for the diameter of the flank organs) as compared to the flank organs from testosterone-treated hamsters. On the other hand, the series of compounds containing a chlorine substituent at C-6 compounds (12a-12d) showed a higher antiandrogenic activity as compared to the compounds lacking a halogen atom at C-6 (14a, 14b and 14d). Although compounds 13 and 15 decreased the flank organs diameter size, however, this increase was not statistically significant as compared to that of the commercially available product finasteride. The steroidal derivatives 13, 14a-14d (lacking the chlorine substituent at C-6) and 15 (having a bromine atom at C-6) exhibited a higher 5α-reductase inhibitory activity (lower IC50 values) as compared to the series of compounds 12a-12d having the halogen substituent at C-6. Finasteride reduced the diameter size of the flank organs. The effect of this steroid and compounds 12a-12d, 13, 14a-14d and 15 on hamster flank organs can be explained by the fact that these steroids did not bind to the androgens receptor, which indicates that its mechanism of action is an inhibiting for the 5α-reductase activity. This enzyme is present in the hamster flank organs and was inhibited by the novel steroids in the human prostate homogenates.
Further syntheses of cyproterone acetate
-
Page/Page column 3; 18; 30; 32, (2010/02/07)
The present invention relates to improved methods for synthesising cyproterone acetate (17α-Acetoxy-6-chloro-1α, 2α-methylene-4,6-pregnadiene-3,20-dione) from solasodine. The methods of the invention are shorter as those of the prior art and therefore more economic.
