Dienogestrel Chemical Properties

Melting point:

210-2140C

alpha 

D25 -290° (c = 0.5 in pyridine)

Boiling point:

451.46°C (rough estimate)

Density 

1.0899 (rough estimate)

refractive index 

1.5614 (estimate)

storage temp. 

2-8°C

solubility 

Chloroform (Slightly), Pyridine (Slightly)

pka

13?+-.0.40(Predicted)

form 

powder

color 

white to beige

optical activity

[α]/D -305 to -325°, c = 1 in dichloromethane

Merck 

14,3106

InChI

InChI=1/C20H25NO2/c1-19-8-6-16-15-5-3-14(22)12-13(15)2-4-17(16)18(19)7-9-20(19,23)10-11-21/h12,17-18,23H,2-10H2,1H3/t17-,18+,19+,20-/s3

InChIKey

AZFLJNIPTRTECV-XAYGXGNENA-N

SMILES

C[C@]12CCC3=C4CCC(=O)C=C4CC[C@@]3([H])[C@]1([H])CC[C@@]2(O)CC#N |&1:1,14,16,20,r|

CAS DataBase Reference

65928-58-7(CAS DataBase Reference)

Safety Information

RTECS 

RC8899500

HS Code 

2937.23.5050

Toxicity

LD50 oral in mouse: 4gm/kg

Dienogestrel Usage And Synthesis

Description

Dienoest is a selective progesterone drug that has been launched in recent years. It can stabilize endometrial tissue by specifically binding to ethylene nortestosterone and progesterone derivatives. Studies have found that tumor necrosis factor (TNF) and interleukin (IL-8) tend to increase in patients with endometriosis.

Pharmacodynamics

Dienogest has progestogenic activity, possibly some antiprogestogenic activity, and has antiandrogenic activity.The medication does not interact with the estrogen receptor, the glucocorticoid receptor, or the mineralocorticoid receptor, and hence has no estrogenic, glucocorticoid, or antimineralocorticoid activity.Because of its relatively high selectivity as a progestogen, dienogest may have favorable safety and tolerability compared to various other progestins.

Features

Dienogest is a mixed progestogen with dual properties of 19-nortestosterone derivatives and progesterone derivatives; therefore, it combines the pharmacological advantages of natural and synthetic progestins with high progestogenic activity .

Side effects

Side effects associated with dienogestrel are the same as those expected of a progestogen.They include menstrual irregularities, headaches, nausea, breast tenderness, depression, acne, weight gain, flatulence, and others.Dienogest produces no androgenic side effects and has little effect on metabolic and lipid hemostatic parameters.

Physical properties

Dienogestrel is a pale yellow solid.

Uses

Derivative of 19-Nortestosterone. In combination with estrogen as oral contraceptive. Progestogen.

Uses

Dienogest is an orally active synthetic progesterone (or progestin). It is available for use as an oral contraceptive in combination with ethinylestradiol. It has antiandrogenic activity and as a result can improve androgenic symptoms.

Definition

ChEBI: A steroid hormone that is 17beta-hydroxy-3-oxoestra-4,9-diene substituted at position 17 by a cyanomethyl group. Used as an oral contraceptive.

brand name

Endometrion (Schering A.G., Germany).

Biochem/physiol Actions

Dienogest is used to treat endometriosis. It might also help to decrease the levels of plasma estradiol by stimulating cell death of granulosa cells in the ovary.

Synthesis

Using 17α-cyanomethyl-17β-hydroxy-estra-5(10)-en-3-one (142 g, 0.45 mol) as raw material, it was dissolved in 850 ml of pyridine, stirred and cooled to 20-25 °C to form a homogeneous solution. Subsequently, a solution of tribrominated pyridine (150 g, 0.47 mol) in 640 ml of pyridine was slowly added and the reaction temperature was controlled to gradually increase to 50 °C. The reaction mixture was stirred continuously at this temperature for 1 hour. After completion of the reaction, the mixture was slowly poured into a stirred mixture consisting of 320 ml of concentrated sulfuric acid and 5600 ml of water to quench the reaction. The precipitated crystals were separated by filtration and dried under vacuum at below 60°C. The crude product was purified by recrystallization from acetone to give 116 g (83% yield) of the final target compound 2-((8S,13S,14S,17R)-17-hydroxy-13-methyl-3-oxo-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl)acetonitrile. The product was analyzed by HPLC showing no less than 97% active ingredient content and no more than 1% impurity of 4-bromo-dienoglucose. The compound has a melting point of 210-213°C and a specific optical rotation [α]20D of -318° (c=1%, dichloromethane).

References

[1] Zeitschrift fur Chemie, 1986, vol. 26, # 10, p. 371 - 371
[2] Patent: WO2007/66158, 2007, A2. Location in patent: Page/Page column 9
[3] Arzneimittel-Forschung/Drug Research, 1980, vol. 30, # 3, p. 401 - 406
[4] Patent: US2010/298585, 2010, A1. Location in patent: Page/Page column 3, 4

Dienogestrel (65928-58-7)Related Product Information

• Dienogest Impurity I
• (17α)-3,3-[1,2-Ethanediylbis(oxy)]-17-hydroxy-19-norpregna-5(10),9(11)-diene-21-nitrile
• DiMethoxy Dienogest
• 9,11-Dehydro-17α-cyanoMethyl Estradiol
• Sts 64
• (17α)-17-Hydroxy-3-oxo-19-norpregna-5(10),9(11)-diene-21-nitrile
• 3,3-DiMethoxyestra-5(10),9(11)-dien-17-one
• 17 alpha-cyanomethyl-19-nortestosterone
• (17α)-4-Bromo-17-hydroxy-3-oxo-19-norpregna-4,9-diene-21-nitrile
• Estra-4,9-diene-3,17-dione
• 19-HYDROXY-4-ANDROSTENE-3,17-DIONE
• Estradiene dione-3-keta
• 17β-Cyanmethyl-oestra-1,3,5(10)-trien-3,17β-diol
• 11β-Hydroperoxy Dienogest
• Dodecanenitrile
• N-HEPTADECANONITRILE
• 3-HYDROXY-3-METHYLBUTYRONITRILE
• ORANILE