Megestrol

Chemical properties

White Solid

The Uses of Megestrol

Megestrol is an orally active progestogen. Megestrol is used in combinations as oral contraceptive and as antineoplastic agent.

Definition

ChEBI: A 3-oxo Delta4-steroid that is pregna-4,6-diene-3,20-dione substituted by a hydroxy group at position 17.

Indications

As a representitive of the compounds of the class of progestins, this drug is used for various forms of cancer, in particular cancer of the breast, kidneys, and others.

brand name

Megace (Bristol-Myers Squibb); Megace (Par);Citestrol;Co-ervonum;Combiquens;Femagest;Kombiquens;Megecat;Megeron;Megestat;Menoquens;Neo-delpregnin;Niaestine;Niagestine;Novaquin;Novokvens;Novolina;Novoquens;Oracolnal;Ovaban;Ovarid;Pallace;Serial 28;Volidan;Volplan.

World Health Organization (WHO)

Megestrol acetate, a synthetic progestogen, was introduced in the early 1960s as a component in oral contraceptive preparations. In 1967, as a result of new regulations required by the United States Food and Drug Administration, megestrol 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 megestrol remains available in some countries for contraceptive purposes. In other countries its use is restricted to anticancer treatment. (Reference: (WHODI) WHO Drug Information, 1-3, 5-7, 1984)

Synthesis

Megestrol, 17|á-hydroxy-6|á-methylpregna-4,6-dien-3,20-dione acetate (28.3.9), is a product of dehydrogenation medroxyprogesterone (28.3.7) with chloranil (tetrachloro-p-benzoquinone) in the presence of p-toluenesulfonic acid, which results in the formation of an additional double bond at position C6¨CC7, and subsequent acetylation of the product (28.3.8) leads to the desired megestrol (28.3.9) by acetic anhydride in the presence of p-toluenesulfonic acid.