Ethynerone (

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), also known as 17α-(2-chloroethynyl)estra-4,9-dien-17β-ol-3-one, is a steroidal progestin of the 19-nortestosterone group that was first reported in 1961 but was never marketed. Under the developmental code name MK-665, it was studied in

combination In mathematics, a combination is a selection of items from a set that has distinct members, such that the order of selection does not matter (unlike permutations). For example, given three fruits, say an apple, an orange and a pear, there are th ...

with mestranol as an

oral contraceptive Oral contraceptives, abbreviated OCPs, also known as birth control pills, are medications taken by mouth for the purpose of birth control. Female Two types of female oral contraceptive pill, taken once per day, are widely available: * The combi ...

. Development of the drug was discontinued due to concerns surrounding toxicity findings in dogs. It is a chloroethynylated derivative of norethisterone. In 1966, during its clinical development, ethynerone was found to produce

mammary gland A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their name from the Latin word ''mamma'', "breast". The mammary glands are arranged in organs such as the breasts in pri ...

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s in dogs treated with it at very high doses for prolonged periods of time. Subsequent investigation found that

17α-hydroxyprogesterone 17α-Hydroxyprogesterone (17α-OHP), also known as 17-OH progesterone (17-OHP), or hydroxyprogesterone (OHP), is an endogenous progestogen steroid hormone related to progesterone. It is also a chemical intermediate in the biosynthesis of many o ...

derivatives included

anagestone acetate Anagestone acetate, sold under the brand names Anatropin and Neo-Novum, is a progestin medication which was withdrawn from medical use due to carcinogenicity observed in animal studies. Medical uses Anagestone acetate was used in combination wit ...

chlormadinone acetate Chlormadinone acetate (CMA), sold under the brand names Belara, Gynorelle, Lutéran, and Prostal among others, is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy, as a component of menopausal hor ...

, medroxyprogesterone acetate, and

megestrol acetate Megestrol acetate (MGA), sold under the brand name Megace among others, is a progestin medication which is used mainly as an appetite stimulant to treat wasting syndromes such as cachexia.https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/ ...

produced similar mammary gland tumors, and that their ability to do so correlated directly with their progestogenic actions. In contrast, the non-halogenated 19-nortestosterone derivatives norgestrel, norethisterone,

noretynodrel Noretynodrel, or norethynodrel, sold under the brand name Enovid among others, is a progestin medication which was previously used in birth control pills and in the treatment of gynecological disorders but is now no longer marketed. It was availa ...

, and

etynodiol diacetate Etynodiol diacetate, or ethynodiol diacetate, sold under the brand names Demulen and Femulen among others, is a progestin medication which is used in birth control pills. The medication is available only in combination with an estrogen. It is t ...

, which are much less potent as progestogens, did not produce such effects at the dosages tested. Clinical development of ethynerone was discontinued, and many of the 17α-hydroxyprogesterone derivatives were withdrawn for the indication of hormonal contraception. Research later on revealed species differences between dogs and humans and established that there is no similar risk in humans.

Synthesis

References

Estranes Organochlorides Progestogens {{steroid-stub

Synthesis

See also

References