18-Methylsegesterone acetate

18-Methylsegesterone acetate (18-methyl-SGA; also known as 18-methylnestorone) is a progestin medication of the 19-norprogesterone group which was never marketed.^[1][2][3] It was first described in a patent in 1997 and then in a literature paper in 2003.^[4][1] 18-Methyl-SGA is the C18 methyl or C13β ethyl derivative of segesterone acetate (SGA; 16-methylene-17α-acetoxy-19-norprogesterone), and shows 3 to 10 times the progestogenic potency of SGA in bioassays.^[1] This is analogous to the case of the 19-nortestosterone progestin norethisterone and its 18-methyl derivative levonorgestrel, the latter showing substantially increased potency relative to the former similarly.^[1] As SGA is already one of the most potent progestins to have been developed, with 100-fold the potency of progesterone and 10-fold the potency of levonorgestrel in bioassays, 18-methyl-SGA is an extremely potent progestogen, among if not the most potent known.^[2][5][1]

18-Methylsegesterone acetate

Clinical data
Other names	18-Methyl-SGA; 13β-Ethyl-SGA; 18-Methylnestorone; 18-Methyl-NES; 13β-Ethylnestorone; 13β-Ethyl-NES; 18-Methylelcometrine; 16-Methylene-17α-acetoxy-18-methyl-19-norprogesterone; 16-Methylene-17α-hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione acetate
Drug class	Progestin; Progestogen; Progestogen ester
Identifiers
IUPAC name [(8R,9S,10R,13S,14S,17R)-17-Acetyl-13-ethyl-16-methylidene-3-oxo-2,6,7,8,9,10,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-17-yl] acetate
PubChem CID	9908093
ChemSpider	8083745
Chemical and physical data
Formula	C24H32O4
Molar mass	384.516 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC[C@]12CC[C@H]3[C@H]([C@@H]1CC(=C)[C@@]2(C(=O)C)OC(=O)C)CCC4=CC(=O)CC[C@H]34
InChI InChI=1S/C24H32O4/c1-5-23-11-10-20-19-9-7-18(27)13-17(19)6-8-21(20)22(23)12-14(2)24(23,15(3)25)28-16(4)26/h13,19-22H,2,5-12H2,1,3-4H3/t19-,20+,21+,22-,23-,24-/m0/s1 Key:YIAUAVGJQYAQFE-ZUYVPRDGSA-N

SGA is a highly selective progestogen.^[1][5] Like SGA, 18-methyl-SGA shows negligible affinity for the androgen receptor.^[1][3] While 18-methyl-SGA has not been assessed at the other steroid hormone receptors, it is expected to be highly selective for the progesterone receptor similarly to SGA.^[1] 18-Methyl-SGA shows over 16 times the affinity of progesterone for the progesterone receptor expressed in rat uterus.^[1] In terms of oral bioavailability, it is known that SGA is not active orally, while the oral activity of 18-methyl-SGA is unknown.^[1] The addition of an 18-methyl group to SGA is unlikely to affect its rate of delivery from sustained release systems.^[1] As such, 18-methyl-SGA should be ideally suited for use via routes of administration like subcutaneous implants and transdermal patches.^[1]