17230-88-5 Usage
Description
Danazol, also known as 17α-pregn-2,4-dien-20-yno-[2,3-d]isoxazol-17-ol, is a synthetic steroid with diverse biological effects. It is a weak androgen and an anabolic steroid derivative of ethisterone, with mild androgenic side effects. Danazol has little estrogenic or progestogenic activity, despite the presence of the 17α-ethinyl group. It binds to sex hormone-binding globulin (SHBG), decreasing the hepatic synthesis of this estradiol and testosterone carrier, which results in an increase in free testosterone. Danazol inhibits the production of FSH and LH by the hypothalamus and pituitary, and it also binds to PRs, GRs, ARs, and ERs. Although its exact mechanism of action is unclear, it is known to alter endometrial tissue, making it inactive and atrophic, which contributes to its effectiveness in treating endometriosis. Danazol is also used to treat hereditary angioedema and fibrocystic breast disease. It is a white solid and is commercially available under the brand name Dancocrine by Sanofi Aventis.
Uses
1. Used in Endometriosis Treatment:
Danazol is used as an anterior pituitary suppressant for the treatment of endometriosis. It alters endometrial tissue, making it inactive and atrophic, which helps in managing the symptoms of endometriosis.
2. Used in Hereditary Angioedema Treatment:
Danazol is used as an antigonadotropin for the treatment of hereditary angioedema, a condition characterized by recurrent episodes of swelling due to the accumulation of fluid in the body's tissues.
3. Used in Fibrocystic Breast Disease Treatment:
Danazol is used as an anterior pituitary suppressant for the treatment of fibrocystic breast disease, a condition that causes lumps or areas of swelling in one or both breasts.
4. Used in the Pharmaceutical Industry:
Danazol is used as a synthetic steroid with diverse biological effects in the pharmaceutical industry, contributing to the development of various medications for different health conditions.
Originator
Danol,Winthrop,UK,1974
Indications
Danazol, a synthetic androgen, has been used to treat the pruritus of primary
biliary cirrhosis, urticaria, and also idiopathic pruritus. It has been used for treatment of pruritus associated with polycythemia
vera and systemic lupus erythematosus.
Manufacturing Process
Danazol was prepared from 4.32 grams of 17α-ethynyl-2-hydroxymethylene4-androsten-17β-ol-3-one, 1.00 gram of hydroxylamine hydrochloride, 1.12
grams of fused sodium acetate and 135 ml of acetic acid. To a 500 ml, 3-
necked flask, equipped with a sealed Hershberg-type stirrer, a reflux
condenser and a stopper, was added the above androstenone derivative in 300
ml of 95% ethanol. Stirring was commenced and a slurry of fused sodium
acetate and hydroxylamine hydrochloride in glacial acetic acid was added.The mixture was refluxed gently on a steam bath for 1? hours. Fifteen
minutes after initiating the reaction, the reaction mixture gave a negative
ferric chloride test. Most of the ethanol and acetic acid were removed by
distillation in vacuo, 300 ml of water and 300 ml of ether were added to the
concentrate, and the mixture was shaken. The layers were separated, the
aqueous layer extracted with fresh ether, and the combined ether extracts
were washed with water, dried over anhydrous sodium sulfate, filtered and
evaporated to dryness in vacuo. The residue was crystallized by trituration
with ether, and the crystals were collected by filtration, washed with hexane
and dried. The mother liquors were concentrated to dryness and dissolved in a
minimum amount of acetone, whereupon a second crop was obtained. The
two crops were combined, dissolved in ethyl acetate, decolorized with
activated charcoal, and recovered by concentration.The mixture was refluxed gently on a steam bath for 1? hours. Fifteen
minutes after initiating the reaction, the reaction mixture gave a negative
ferric chloride test. Most of the ethanol and acetic acid were removed by
distillation in vacuo, 300 ml of water and 300 ml of ether were added to the
concentrate, and the mixture was shaken. The layers were separated, the
aqueous layer extracted with fresh ether, and the combined ether extracts
were washed with water, dried over anhydrous sodium sulfate, filtered and
evaporated to dryness in vacuo. The residue was crystallized by trituration
with ether, and the crystals were collected by filtration, washed with hexane
and dried. The mother liquors were concentrated to dryness and dissolved in a
minimum amount of acetone, whereupon a second crop was obtained. The
two crops were combined, dissolved in ethyl acetate, decolorized with
activated charcoal, and recovered by concentration.
Therapeutic Function
Anterior pituitary suppressant
Biological Activity
danazol showed weak androgenic effects.danazol is a derivative of testosterone and ethisterone. an androgen is any natural or synthetic agent stimulating or controling the development and maintenance of male characteristics by binding to androgen receptors. this includes the activity of the primary male sex organs and development of male secondary sex characteristics.
Biochem/physiol Actions
Danazol is a weak androgen; anterior pituitary suppressant.
Side effects
Danazol, a synthetic analogue of 17α-ethynyl testosterone, induces amenorrhea, anovulation and endometrial atrophy via suppression of the hypothalamicpituitary-ovary (HPO) axis. This causes an estrogen-deficient state, but it also causes an increase in androgen production. Danazol generally is not well tolerated because of its androgenic and anabolic side effects, including acne, decreased breast size, facial hair, weight gain, and oily skin. This type of therapy is not a viable option for women with liver disease or hyperlipidemia. Because danazol is teratogenic , it is recommended that effective contraception be utilized during treatment.
Veterinary Drugs and Treatments
Because of expense and unpredictable efficacy, danazol is not commonly
used in veterinary medicine, but has been used as adjunctive
therapy (with corticosteroids) in the treatment of canine immunemediated
thrombocytopenia and hemolytic anemia,
particularly
if the patient becomes refractory to glucocorticoids and other immunosuppressive
therapy. There is apparently synergism when danazol
is combined with corticosteroids for these indications.
Once
remission is attained, some dogs may have their dosage reduced or
other medications may be eliminated and be controlled with danazol
alone. In humans, danazol has been used for the treatment of endometriosis,
fibrocystic breast disease, idiopathic thrombocytopenic
purpura and a variety of other conditions.
in vitro
previous study found that danazol as low as 1 micrometer could suppress lh-stimulated testosterone and androstenedione production in cultured leydig cells. the addition of danazol to a preparation of testicular microsomes elicited a type i cytochrome p-450 binding spectrum. danazol could inhibit progesterone and 17alpha-hydroxy-progesterone binding to microsomal p-450 [1].
in vivo
the purpose of a previous study was to examine the role of androgen and estrogen receptors in danazol suppression of luteinizing hormone (lh) in the rat. the estrogen receptor antagonist, ly 156758, partially antagonized the suppressed levels of lh after administration of danazol to ovariectomized rats. in contrast, the androgen receptor antagonist, flutamide, had no effect on suppressed lh levels after danazol treatment, but did partially reverse the inhibition of lh 24 hr after danazol administration to ovariectomized rats [2].
references
[1] barbieri rl, canick ja, ryan kj. danazol inhibits steroidogenesis in the rat testis in vitro. endocrinology. 1977 dec;101(6):1676-82.[2] snyder bw, beecham gd, winneker rc. danazol suppression of luteinizing hormone in the rat: evidence for mediation by both androgen and estrogen receptors. proc soc exp biol med. 1990 may;194(1):54-7. [3] cole rm, raghavan d, caterson i, teriana n, pearson b, boulas j, rosen m. danazol treatment of advanced prostate cancer: clinical and hormonal effects. prostate. 1986;9(1):15-20.
Check Digit Verification of cas no
The CAS Registry Mumber 17230-88-5 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,7,2,3 and 0 respectively; the second part has 2 digits, 8 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 17230-88:
(7*1)+(6*7)+(5*2)+(4*3)+(3*0)+(2*8)+(1*8)=95
95 % 10 = 5
So 17230-88-5 is a valid CAS Registry Number.
InChI:InChI=1/C22H27NO2/c1-4-22(24)10-8-18-16-6-5-15-11-19-14(13-23-25-19)12-20(15,2)17(16)7-9-21(18,22)3/h1,11,13,16-18,24H,5-10,12H2,2-3H3/t16-,17+,18+,20?,21?,22+/m1/s1
17230-88-5Relevant articles and documents
Process for the preparation of danazol
-
, (2019/02/04)
The invention discloses preparation methods of danazol and an intermediate thereof. The preparation method of danazol is prepared by the steps of taking androstenedione as a starting raw material, and carrying out 3-site enol etherification, 17-site carbonyl ethinylation, 3-site hydrolysis, 2-site methylidynel hydroxylation and oximation to obtain danazol. The 3-site enol etherification comprises firstly carrying out a reaction of androstenedione and triethyl orthoformate for 4-10 h in the presence of absolute ethyl alcohol and p-toluenesulfonic acid and at the temperature of 30-50 DEG C, then adding triethylamine at the temperature of 0-10 DEG C, and continuing to carry out a reaction for 0.2-1 h; the 17-site carbonyl ethinylation comprises firstly carrying out a reaction of a potassium hydroxide powder for 1-2 h in an acetylene airflow and at the temperature of 5-10 DEG C, and then carrying out a reaction with the 3-site enol etherified product for 2-4 h in the presence of tetrahydrofuran and a catalyst, at the temperature of 15-30 DEG C and in the acetylene airflow. The 3-site enol etherification is mild in reaction conditions and relatively high in yield, and the 17-site carbonyl ethynylation is relatively high in reaction yield and relatively short in time.
Process for preparing pregn-20-yne compounds and novel product produced thereby
-
, (2008/06/13)
A process for preparing 17β-hydroxysteroido[2,3-d]isoxazoles substituted at the 17α-position by an ethynyl or substituted ethynyl group comprising reacting a 17-oxosteroido[2,3-d]isoxazole with the appropriate ethynylmagnesium halide, substituted ethynylmagnesium halide, monolithium acetylide or substituted monolithium acetylide. The process affords a novel compound, 21-trifluoromethyl-17α-pregn-4-en-20-yno[2,3-d]isoxazol-17-ol, which has estrogenic activity.
