Chlormadinone acetate Chemical Properties

Melting point:

212°C

alpha 

D +6° (c = 1 in CHCl3)

Boiling point:

512.5±50.0 °C(Predicted)

Density 

1.1345 (estimate)

storage temp. 

Sealed in dry,Store in freezer, under -20°C

solubility 

Chloroform (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly)

form 

Solid

color 

Off-White to Light Yellow

λmax

285nm(EtOH)(lit.)

Merck 

14,2102

BRN 

2633614

NIST Chemistry Reference

Chlormadinone acetate(302-22-7)

EPA Substance Registry System

Pregna-4,6-diene-3,20-dione, 17-(acetyloxy)-6-chloro- (302-22-7)

Safety Information

Hazard Codes 

T

Risk Statements 

60-61-40-48

Safety Statements 

53-22-36/37/39-45

WGK Germany 

3

RTECS 

TU3750000

HS Code 

29372390

Hazardous Substances Data

302-22-7(Hazardous Substances Data)

Toxicity

mouse,LD50,intraperitoneal,3gm/kg (3000mg/kg),ENDOCRINE: ADRENAL CORTEX HYPOPLASIABEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY),Kiso to Rinsho. Clinical Report. Vol. 11, Pg. 571, 1977.

MSDS

• Language:English Provider:SigmaAldrich

Chlormadinone acetate Usage And Synthesis

Description

Chlormadinone acetate is a synthetic progestin. It binds to progesterone, androgen, and glucocorticoid receptors in vitro (K_is = 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

Orally active progesteron with antiandrogenic activity; has been used in combinations as an oral contraceptive. Progestogen; antineoplastic (hormonal).

Uses

tranquilizer, neuroleptic, alpha adrenergic blocker

Definition

ChEBI: Chlormadinone acetate is a corticosteroid hormone.

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.

Chlormadinone acetate (302-22-7)Related Product Information

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