Megestrol acetate Chemical Properties

Melting point:

214°C

Boiling point:

431.17°C (rough estimate)

alpha 

D24 +5° (chloroform)

Density 

1.0474 (rough estimate)

refractive index 

11 ° (C=2, CHCl3)

storage temp. 

Sealed in dry,Room Temperature

solubility 

Practically insoluble in water, soluble in acetone, sparingly soluble in alcohol.

color 

White

Merck 

14,5805

BRN 

1917291

InChIKey

RQZAXGRLVPAYTJ-GQFGMJRRSA-N

SMILES

C1(=O)C=C2[C@](C)(CC1)[C@]1([H])[C@]([H])([C@@]3([H])[C@@](CC1)(C)[C@@](OC(C)=O)(C(=O)C)CC3)C=C2C

CAS DataBase Reference

595-33-5(CAS DataBase Reference)

NIST Chemistry Reference

Megestrol acetate(595-33-5)

EPA Substance Registry System

Megestrol acetate (595-33-5)

Safety Information

Hazard Codes 

Xn

Risk Statements 

40-48

Safety Statements 

22-24/25

WGK Germany 

3

RTECS 

TU4075000

HS Code 

29372390

Toxicity

LD50 intravenous in mouse: 56mg/kg

MSDS

• Language:English Provider:SigmaAldrich

Megestrol acetate Usage And Synthesis

Description

Megestrol Acetate is the acetate salt form of megestrol, a synthetic derivative of the naturally occurring female sex hormone progesterone with potential anti-estrogenic and antineoplastic activity. It is frequently used in the treatment of patients with metastatic breast cancer. It is generally well tolerated, except that it may cause undesirable weight gain. Subsequently, it was shown that megestrol acetate produced weight gain in a variety of cachectic cancer patients. Significant reduction inserum levels of IL-1a and b,IL-2,IL-6, and TNF-o were observed in cancer patientstreated with megestrol acetate which may bear on the mechanism of improved appetite and body weight gain.It has also been postulated that the effect is, at least in part,mediated by NPY,a potent central appetite stimulant.

Chemical Properties

Crystalline Solid

Originator

Megestat,Bristol,W. Germany,1964

Uses

Megestrol acetate USP (Megace) is used to treat Carcinoma of the breast or endorometrium.

Uses

Megestrol acetate (Megace), a semi-synthetic progestational steroid, is the most effective known appetite stimulant at present. Previously used in patients with cancer and acquired immunodeficiency syndrome, only a few studies have considered the applicability of this drug in malnourished older persons.
Megestrol acetate is useful if profound anorexia is the main manifestation of cachexia and if expected survival is weeks to months. Megace has been shown to significantly increase appetite, but not survival. In patients with a shorter predicted survival, a brief course of corticosteroids may be useful to stimulate appetite and have positive effects on nausea, pain, and asthenia.

Definition

ChEBI: Megestrol acetate is a steroid ester resulting from the formal condensation of the hydroxy group of megestrol with the carboxy group of acetic acid. It is an appetite stimulant used for the treatment of anorexia and cachexia. Also used for birth control and for the treatment of breast cancer. It has a role as an antineoplastic agent, an appetite enhancer, a contraceptive drug, a progestin and a synthetic oral contraceptive. It is a steroid ester, an acetate ester, a 20-oxo steroid and a 3-oxo-Delta(4) steroid. It derives from a megestrol.

Manufacturing Process

The following preparation is given in US Patent 3,356,573. 17α-Acetoxy-3βhydroxy-6-methylpregn-5-ene-20-one (1 g), aluminum tert-butoxide (1 g) and p-benzoquinone (6 g) were dissolved in dry benzene (100 ml) and the mixture was heated under reflux for 30 minutes. The reaction mixture was cooled and washed with potassium hydroxide solution until the benzene layer was colorless. The benzene was washed with water, dried and evaporated to dryness under reduced pressure. The residue crystallized from aqueous methanol to give 17α-acetoxy-6-methylpregna-4,6-diene-3,20-dione, needles, MP 214° to 216°C.

brand name

Megace (Bristol-Myers Squibb); Megace (Par).

Therapeutic Function

Cancer chemotherapy

General Description

Megestrol acetate, 17-hydroxy-6-methylpregna-4,6-diene-3,20-dione acetate(Megace), is a progestin used primarily for the palliativemanagement of recurrent, inoperable, or metastatic endometrialor breast carcinoma. Megestrol acetate has also beenindicated for appetite enhancement in patients with AIDS.The biochemical basis for this use of megestrol is unclear.

Clinical Use

Progestin activity is further enhanced when a double bond is introduced between positions 6 and 7, as is found in megestrol acetate. Megestrol is used primarily in the treatment of breast and endometrial carcinomas and in postmenopausal women with advanced hormone-dependent carcinoma.

Safety Profile

Suspected carcinogen with experimental carcinogenic and teratogenic data. Poison by intravenous route. Human reproductive effects bp ingestion and implant routes: effects on ovaries and fallopian tubes, menstrual cycle changes, and female fertility index changes. Mutation data reported. Experimental reproductive effects. When heated to decomposition it emits acrid smoke and irritating fumes. An FDA proprietary drug used to treat endometriosis and breast cancer. A steroid.

Veterinary Drugs and Treatments

Megestrol acetate (Ovaban?—Schering) is approved by FDA for use in dogs only for the postponement of estrus and the alleviation of false pregnancy. In male dogs, it has been used for benign prostatic hypertrophy. It is used clinically for many dermatologic and behavior- related conditions, primarily in the cat. See the Dosage section for specific indications and dosages for both dogs and cats.
Megestrol acetate is indicated in humans for the palliative treatment of advanced carcinoma of the breast or endometrium.

Metabolism

Less than 10% of an oral dose undergoes metabolism. Several major metabolites appear in the urine (e.g., 2-hydroxy and 6-hydroxymethyl megestrol and their glucuronide conjugates).

storage

Store at RT

References

[1] zhang k1, chow pk. the effect of megestrol acetate on growth of hepg2 cells in vitro and in vivo. clin cancer res. 2004 aug 1; 10(15):5226-32.

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