Noretynodrel

Noretynodrel

Clinical data
Trade names	Enovid, Enovid-E, Enovid-E 21, Enavid (all with mestranol)
ATC code	G03FA09 (WHO)
Identifiers
IUPAC name (8R,9S,13S,14S,17R)-17-ethynyl-17-hydroxy-13-methyl-1,2,4,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one
Synonyms	NSC-15432
CAS Number	68-23-5 N
PubChem CID	6231
ChemSpider	5995 Y
UNII	88181ACA0M
ChEMBL	CHEMBL1387 Y
ECHA InfoCard	100.000.620
Chemical and physical data
Formula	C20H26O2
Molar mass	298.419 g/mol
3D model (Jmol)	Interactive image
SMILES O=C4CCC\1=C(\CC[C@@H]2[C@@H]/1CC[C@]3([C@H]2CC[C@]3(C#C)O)C)C4
InChI InChI=1S/C20H26O2/c1-3-20(22)11-9-18-17-6-4-13-12-14(21)5-7-15(13)16(17)8-10-19(18,20)2/h1,16-18,22H,4-12H2,2H3/t16-,17-,18+,19+,20+/m1/s1 Y Key:ICTXHFFSOAJUMG-SLHNCBLASA-N Y
NY (what is this?)

Noretynodrel (INN), or norethynodrel (USAN, BAN), also known as 17α-ethynyl-19-nor-5(10)-testosterone or as 5(10)-norethisterone, is a steroidal progestin of the 19-nortestosterone group and an isomer of norethisterone. Noretynodrel was introduced in 1957 in Enovid, a combination formulation of noretynodrel and mestranol, for the treatment of gynecological and menstrual disorders. A few years later, in May 1960, Enovid was also approved as the first oral contraceptive.

Noretynodrel, unlike most progestins but similarly to etynodiol diacetate, has some estrogenic activity. It has little or no androgenic activity. The drug is a relatively weak progestogen, with only about one-tenth of the progestogenic activity of norethisterone, and in relation to this fact, is no longer used in oral contraceptives.

Noretynodrel is very closely related to norethisterone and tibolone, which are the Δ⁴-isomer and the 7α-methyl derivative of noretynodrel, respectively. Noretynodrel is metabolized in a very similar manner to tibolone, whereas the metabolism of norethisterone differs. Both noretynodrel and tibolone are transformed into 3α- and 3β-hydroxylated metabolites and a Δ⁴-isomer metabolite (in the case of noretynodrel, this being norethisterone), whereas norethisterone is not 3α- or 3β-hydroxylated (and of course does not form a Δ⁴-isomer metabolite). The major metabolites of noretynodrel are 3α-hydroxynoretynodrel and to a lesser extent 3β-hydroxynoretynodrel, formed by 3α- and 3β-hydroxysteroid dehydrogenases (AKR1C1–4), while the Δ⁴-isomer norethisterone is a minor metabolite formed in small amounts. Tibolone is considered to be a prodrug into both its 3α- and 3β-hydroxylated and Δ⁴-isomerized metabolites. Noretynodrel is also thought to be a prodrug, as it is rapidly metabolized and cleared from circulation (within 30 minutes) and shows very weak relative affinity for the progesterone receptor (PR), although noretynodrel appears to form norethisterone in only minor quantities.