Ethynerone (INN, USAN), 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.[1] Under the developmental code name MK-665, it was studied in combination with mestranol as an oral contraceptive.[2] Development of the drug was discontinued due to concerns surrounding toxicity findings in dogs.[2] It is a chloroethynylated derivative of norethisterone.[3]
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| Routes of administration | Oral |
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| Formula | C20H23ClO2 |
| Molar mass | 330.85 g·mol−1 |
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In 1966, during its clinical development, ethynerone was found to produce mammary gland tumors in dogs treated with it at very high doses for prolonged periods of time.[4][5][6] Subsequent investigation found that 17α-hydroxyprogesterone derivatives included anagestone acetate, chlormadinone acetate, medroxyprogesterone acetate, and megestrol acetate produced similar mammary gland tumors, and that their ability to do so correlated directly with their progestogenic actions.[6][7] In contrast, the non-halogenated 19-nortestosterone derivatives norgestrel, norethisterone, noretynodrel, and etynodiol diacetate, which are much less potent as progestogens, did not produce such effects at the dosages tested.[6] Clinical development of ethynerone was discontinued, and many of the 17α-hydroxyprogesterone derivatives were withdrawn for the indication of hormonal contraception.[6][7] Research later on revealed species differences between dogs and humans and established that there is no similar risk in humans.[2]
Synthesis
