18-Methylsegesterone acetate

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;
CompTox Dashboard (EPA)	DTXSID901336364 ;
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;

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]

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]

Comparison of potencies of selected progestogens in animals
Progestogen	PRTooltip Progesterone receptor RBATooltip Relative binding affinity (rat uterus)	Clauberg assay^a	Pregnancy maintenance
18-Methyl-SGA	355%	0.3 μg	0.03 mg
Segesterone acetate	107%	1 μg	0.3 mg
Levonorgestrel	100%	3 μg	0.3 mg
Progesterone	22%	100 μg	1.0 mg
Footnotes: ^a = Minimum effective dose. Sources: ^[1]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m Tuba Z, Bardin CW, Dancsi A, Francsics-Czinege E, Molnár C, Csörgei J, Falkay G, Koide SS, Kumar N, Sundaram K, Dukát-Abrók V, Balogh G (May 2000). "Synthesis and biological activity of a new progestogen, 16-methylene-17alpha-hydroxy-18-methyl-19-norpregn-4-ene-3, 20-dione acetate". Steroids. 65 (5): 266–74. doi:10.1016/S0039-128X(99)00109-9. PMID 10751638. S2CID 37188669.
^ ^a ^b Sitruk-Ware R, Small M, Kumar N, Tsong YY, Sundaram K, Jackanicz T (November 2003). "Nestorone: clinical applications for contraception and HRT". Steroids. 68 (10–13): 907–13. doi:10.1016/S0039-128X(03)00140-5. PMID 14667982. S2CID 34984413.
^ ^a ^b Kumar N, Fagart J, Liere P, Mitchell SJ, Knibb AR, Petit-Topin I, Rame M, El-Etr M, Schumacher M, Lambert JJ, Rafestin-Oblin ME, Sitruk-Ware R (January 2017). "Nestorone as a Novel Progestin for Nonoral Contraception: Structure-Activity Relationships and Brain Metabolism Studies". Endocrinology. 158 (1): 170–182. doi:10.1210/en.2016-1426. PMC 5412978. PMID 27824503.
^ 18-methyl 16-methylene 19-nor pregnane derivatives as progestins, pharmaceutical compositions containing them and process for the preparation thereof. https://patents.google.com/patent/WO1997023498A1/en
^ ^a ^b Kumar N, Koide SS, Tsong Y, Sundaram K (2000). "Nestorone: a progestin with a unique pharmacological profile". Steroids. 65 (10–11): 629–36. doi:10.1016/S0039-128X(00)00119-7. PMID 11108869. S2CID 13722269.

[pmid10751638-1] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m Tuba Z, Bardin CW, Dancsi A, Francsics-Czinege E, Molnár C, Csörgei J, Falkay G, Koide SS, Kumar N, Sundaram K, Dukát-Abrók V, Balogh G (May 2000). "Synthesis and biological activity of a new progestogen, 16-methylene-17alpha-hydroxy-18-methyl-19-norpregn-4-ene-3, 20-dione acetate". Steroids. 65 (5): 266–74. doi:10.1016/S0039-128X(99)00109-9. PMID 10751638. S2CID 37188669.

[pmid14667982-2] Sitruk-Ware R, Small M, Kumar N, Tsong YY, Sundaram K, Jackanicz T (November 2003). "Nestorone: clinical applications for contraception and HRT". Steroids. 68 (10–13): 907–13. doi:10.1016/S0039-128X(03)00140-5. PMID 14667982. S2CID 34984413.

[pmid27824503-3] Kumar N, Fagart J, Liere P, Mitchell SJ, Knibb AR, Petit-Topin I, Rame M, El-Etr M, Schumacher M, Lambert JJ, Rafestin-Oblin ME, Sitruk-Ware R (January 2017). "Nestorone as a Novel Progestin for Nonoral Contraception: Structure-Activity Relationships and Brain Metabolism Studies". Endocrinology. 158 (1): 170–182. doi:10.1210/en.2016-1426. PMC 5412978. PMID 27824503.

[WO1997023498A1-4] 18-methyl 16-methylene 19-nor pregnane derivatives as progestins, pharmaceutical compositions containing them and process for the preparation thereof. https://patents.google.com/patent/WO1997023498A1/en

[pmid11108869-5] Kumar N, Koide SS, Tsong Y, Sundaram K (2000). "Nestorone: a progestin with a unique pharmacological profile". Steroids. 65 (10–11): 629–36. doi:10.1016/S0039-128X(00)00119-7. PMID 11108869. S2CID 13722269.

[1]

[2]

[3]

[4]

[5]

See also

References