Acetomepregenol

Acetomepregenol
Clinical data
Trade names	Diamol
Other names	ACM; Mepregenol diacetate; Diamol; Megestrol diacetate; Megestrol 3β,17α-diacetate; 3β,17α-Diacetoxy-6-methylpregna-4,6-dien-20-one; 6-Methylpregna-4,6-dien-3β,17α-diol-20-one diacetate
Drug class	Progestogen; Progestin; Progestogen ester
Identifiers
	IUPAC name [(3S,8R,9S,10R,13S,14S,17R)-17-acetyl-17-acetyloxy-6,10,13-trimethyl-1,2,3,8,9,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-yl] acetate;
CAS Number	3116-07-2;
PubChem CID	197015;
ChemSpider	170630;
UNII	1JI0G99BDO;
CompTox Dashboard (EPA)	DTXSID40953248 ;
Chemical and physical data
Formula	C26H36O5
Molar mass	428.569 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=CC2C(CCC3(C2CCC3(C(=O)C)OC(=O)C)C)C4(C1=CC(CC4)OC(=O)C)C;
	InChI InChI=1S/C26H36O5/c1-15-13-20-21(24(5)10-7-19(14-23(15)24)30-17(3)28)8-11-25(6)22(20)9-12-26(25,16(2)27)31-18(4)29/h13-14,19-22H,7-12H2,1-6H3/t19-,20+,21-,22-,24+,25-,26-/m0/s1; Key:SDHHPVPFUVQWKY-AVHYYFBHSA-N;

Acetomepregenol (ACM), also known as mepregenol diacetate and sold under the brand name Diamol, is a progestin medication which is used in Russia for the treatment of gynecological conditions and as a method of birth control in combination with an estrogen.^[1]^[2]^[3]^[4]^[5]^[6]^[7] It has also been studied in the treatment of threatened abortion.^[3] It has been used in veterinary medicine as well.^[8]^[9]^[10] It has been marketed since at least 1981.^[8]^[9]^[10]

Pharmacology

Based on its chemical structure, namely the lack of a C3 ketone, it is probable that acetomepregenol is a prodrug of megestrol acetate (the 3-keto analogue).^[11]^[12]

Chemistry

Acetomepregenol, also known as megestrol 3β,17α-diacetate, as well as 3β-dihydro-6-dehydro-6-methyl-17α-hydroxyprogesterone diacetate or as 3β,17α-diacetoxy-6-methylpregna-4,6-dien-20-one, is a synthetic pregnane steroid and a derivative of progesterone and 17α-hydroxyprogesterone.^[3]^[4]^[7] It is very close to megestrol acetate (6-dehydro-6-methyl-17α-acetoxyprogesterone) in structure, except that there is a hydroxyl group with an acetate ester attached at the C3 position instead of a ketone.^[3]^[4]^[7] A closely related medication is cymegesolate (also known as megestrol 3β-cypionate 17α-acetate), which, in contrast, has not been marketed.^[13]^[14]

References

^ Korkhov VV (1985). "[Current trends in the development of oral contraception]". Farmakologiia I Toksikologiia (in Russian). 48 (4): 119–122. PMID 3899717.
^ Nikitina GV, Savchenko ON, Stepanov MG (1987). "[Hormonal properties of new 17 alpha-hydroxyprogesterone derivatives]". Problemy Endokrinologii (in Russian). 33 (3): 60–63. PMID 3116530.
^ ^a ^b ^c ^d Sidel'nikova VM, Demidova EM, Borisova I, Dondukova TM, Absava GI, Korkhov VV (September 1990). "[The use of acetomepegrenol in the therapy of threatened abortion]". Akusherstvo I Ginekologiia (in Russian) (9): 37–40. PMID 2278305.
^ ^a ^b ^c Grinenko GS, Popova EV, Korkhov VV, Lesik EA, Petrosyan MA, Topil'skaya NI (March 2000). "Synthesis and biological activity of 17α-acetoxy-3β-phenylpropionyloxy-6-methylpregna-4,6-dien-20-one". Pharmaceutical Chemistry Journal. 34 (3): 113–114. doi:10.1007/BF02524577. ISSN 1573-9031. S2CID 44235508. Note that 3,17-diacetoxy-6-methylpregna-4,6-dien-20-one (1b), a structural analog of compound 1a, is certified in Russia under the trade name acetomepregnol and recommended for therapeutic purposes in gynecological practice and as a contraceptive preparation in combination with estrogens [4].
^ Mashkovskii MD (December 2000). "Eightieth Anniversary of the Drug Chemistry Center/All-Russian Pharmaceutical Chemistry Scientific Research Institute". Pharmaceutical Chemistry Journal. 34 (12): 677–680. doi:10.1023/A:1010416205068. ISSN 1573-9031. S2CID 24703856.
^ Sergeev PV, Rzheznikov VM, Korkhov VV, Grinenko GS, Semeikin AV, Mayatskaya EE, et al. (July 2005). "Investigation of the gestagen activity of 17α-acetoxy-3β-butanoyloxy-6-methylpregna-4, 6-dien-20-one". Pharmaceutical Chemistry Journal. 39 (7): 358–360. doi:10.1007/s11094-005-0154-4. S2CID 35450212. Gestagens are widely used in medicine as drugs for the treatment of breast and uterine tumors, endometriosis, uterine bleeding, and premenstrual syndrome, as a means of hormonal therapy and maintenance of pregnancy, and as contraceptives [1, 2]. In clinics, drugs of this group are represented by acetomepregenol (AMP), medroxyprogesterone acetate (MPA), levonorgestrel, progesterone, didrogesterone, etc. [1].
^ ^a ^b ^c Zeinalov OA, Yaderets VV, Stytsenko TS, Petrosyan MA, Andryushina VA (July 2012). "Synthesis and biological activity of synthetic 17α-hydroxyprogesterone derivatives". Pharmaceutical Chemistry Journal. 46 (4): 203–206. doi:10.1007/s11094-012-0761-9. ISSN 1573-9031. S2CID 7159432.
^ ^a ^b Bratanov K, Bankov N, Doichev S, Pisheva M, Klinskii IU, Zhirkov G (1981). Action of diacetate mepregnol (diamol) on estrus induction in sheep in physiological anestrus. Reguliatsiia i intensifikatsiia protsessov razmnozheniia sel'skokhoziaistvennykh zhivotnykh: trudy Mezhdunarodnogo simpoziuma, sostoiavshegosia v Sofii, mai 1980 godina/[red. koll.: K. Bratanov (otvet. red.)... i dr.]
^ ^a ^b Zhirkov GF (1981). "Testing diamol on sheep on a fattening farm". Biulleten'nauchnykh Rabot-Vsesoiuznyi Nauchno-issledovatel'skii Institut Zhivotnovodstva.
^ ^a ^b Klinskii I, Zhirkov GF (January 1982). "[Use of mepregenol diacetate (Diamol), a gestagen preparation, for estrus synchronization in caracul sheep during mating season]". Archiv Fur Experimentelle Veterinarmedizin (in Russian). 36 (1): 159–162. PMID 7201304.
^ Ian S. Fraser (1998). Estrogens and Progestogens in Clinical Practice. Churchill Livingstone. p. 281. ISBN 978-0-443-04706-0. Progestational activity depends on the presence of a 3-keto group in ring A of the steroid skeleton. Most of the progestogens used today do indeed carry such a group in their original molecules. However, the 3-keto group is initially missing in the case of desogestrel and norgestimate. They are prodrugs which undergo metabolic conversion to active 3-keto derivatives in the body.
^ McRobb L, Handelsman DJ, Kazlauskas R, Wilkinson S, McLeod MD, Heather AK (May 2008). "Structure-activity relationships of synthetic progestins in a yeast-based in vitro androgen bioassay". The Journal of Steroid Biochemistry and Molecular Biology. 110 (1–2): 39–47. doi:10.1016/j.jsbmb.2007.10.008. PMID 18395441. S2CID 5612000. Prodrugs (lack 3-keto): Ethylestrenol, Lynestrenol, Ethynodiol, Allylestrenol, Norgestimate
^ De-Wei Z (1982). "Research activities in the field of oral contraceptives in the People's Republic of China". Acta Obstetricia et Gynecologica Scandinavica. Supplement. 105: 51–60. doi:10.3109/00016348209155319. PMID 6952745. S2CID 44858028.
^ Yang YC, Gu XG, Li SX (1982). "Antifertility Effect of a Long-Acting Progestin (3-Cyclopentyl Propionate of Megestrol Acetate): Prematurity of the Endometrium and Accompanying Changes of Uteroglobin and Progesterone in Uterine Fluid". Proteins and Steroids in Early Pregnancy. pp. 335–342. doi:10.1007/978-3-642-67890-5_22. ISBN 978-3-642-67892-9.