Cymegesolate - Wikiwand

Cymegesolate (developmental code name Progestin No. 1), also known as cypionyl megestrol acetate or as megestrol acetate 3β-cypionate, is a progestin medication which was never marketed.^[1]^[2]^[3]^[4]^[5]^[6] It was developed in China in the late 1970s and early to mid 1980s for use as a hormonal contraceptive.^[1]^[2]^[3]^[4]^[5]^[6] The medication was formulated at a dose of 50–100 mg in combination with a "trace" dose of 0.25–0.5 mg quinestrol as a long-lasting, once-a-month combined oral contraceptive pill.^[1]^[2] This combination has been studied in 1,213 women across a total of 9,651 menstrual cycles, with contraceptive effectiveness of over 99.13% and "very few side effects."^[1] At the high dose (100 mg / 0.5 mg), it showed an anovulation rate of only about 60%, and instead mediated its contraceptive effects via a marked anti-implantation effect.^[2]

Other namesCypionyl megestrol acetate; Megestrol acetate 3β-cypionate; Megestrol acetate 3β-cyclopentylpropionate; Progestin No. 1; Progestin I; Progestagen I; 17α-Acetoxy-6-dehydro-6-methylprogesterone 3β-cypionate; 17α-Acetoxy-6-methylpregna-4,6-diene-3,20-dione 3β-cypionate

Routes of
administrationBy mouth^[1]^[2]

Drug classProgestin; Progestogen; Progestogen ester

CAS Number

72648-88-5^Y

Quick facts Clinical data, Other names ...

Cymegesolate
Clinical data

Other names	Cypionyl megestrol acetate; Megestrol acetate 3β-cypionate; Megestrol acetate 3β-cyclopentylpropionate; Progestin No. 1; Progestin I; Progestagen I; 17α-Acetoxy-6-dehydro-6-methylprogesterone 3β-cypionate; 17α-Acetoxy-6-methylpregna-4,6-diene-3,20-dione 3β-cypionate
Routes of administration	By mouth^[1]^[2]
Drug class	Progestin; Progestogen; 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] 3-cyclopentylpropanoate
CAS Number	72648-88-5^Y
PubChem CID	126290
ChemSpider	112247
UNII	4D9TFH8PLX
CompTox Dashboard (EPA)	DTXSID70993490
Chemical and physical data
Formula	C₃₂H₄₆O₅
Molar mass	510.715 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CC1=C[C@@H]2[C@H](CC[C@]3([C@H]2CC[C@@]3(C(=O)C)OC(=O)C)C)[C@@]4(C1=C[C@H](CC4)OC(=O)CCC5CCCC5)C
InChI InChI=1S/C32H46O5/c1-20-18-25-26(13-16-31(5)27(25)14-17-32(31,21(2)33)37-22(3)34)30(4)15-12-24(19-28(20)30)36-29(35)11-10-23-8-6-7-9-23/h18-19,23-27H,6-17H2,1-5H3/t24-,25+,26-,27-,30+,31-,32-/m0/s1 Key:WAHQVRCNDCHDIB-QZYSPNBYSA-N

Chemistry

Cymegesolate, also known as megestrol acetate 3β-cypionate, as well as 17α-acetoxy-6-dehydro-6-methylprogesterone 3β-cyclopentylpropionate or 17α-acetoxy-6-methylpregna-4,6-diene-3,20-dione 3β-cyclopentylpropionate, is a synthetic pregnane steroid and a derivative of progesterone and 17α-hydroxyprogesterone.^[1]^[2] It is the C3β cypionate (cyclopentylpropionate) ester of megestrol acetate.^[1]^[2] A closely related medication is acetomepregenol (mepregenol diacetate; also known as megestrol 3β,17α-diacetate), which, in contrast, has been marketed.^[7]^[8]^[9]^[10]

References

[1]
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.
[2]
Yang YC, Gu XG, Li SX (1982). Proteins and Steroids in Early Pregnancy. pp. 335–342. doi:10.1007/978-3-642-67890-5_22. ISBN 978-3-642-67892-9.
[3]
Chi-ming, L. (1983). New Long Acting Contraceptive Progestagen Studies on Synthesis of “Cymegesolate”[J]. Reproduction & Contraception, 4, 011.
[4]
Yang YQ, Li SX, Gu XG (August 1985). "[Effect of progestin no. 1 (cymegesolate) on menstrual cycles and plasma levels of progesterone in rhesus monkeys]". Sheng Li Xue Bao (in Chinese). 37 (4): 368–373. PMID 3837333.
[5]
Wu JZ, Yun XJ, Wu MZ, Shen HY, Wang AL (February 1983). "[Clinical study of a long-acting progestogen contraceptive 3-cyclopentyl propionate of megestrol acetate (progestin no. 1)]". Sheng Zhi Yu Bi Yun = Reproduction and Contraception (in Chinese). 3 (2): 36–38. PMID 12339176.
[6]
Xue-jing, W. J. Z. Y., & Mo-zhen, W. (1983). Clinical Study of a Long-Acting Progestogen Contraceptive 3-Cyclopentyl Propionate of Megestrol Acetate (Progestin No. 1)[J]. Reproduction & Contraception, 2, 009.
[7]
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.
[8]
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].
[9]
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.
[10]
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. ISSN 1573-9031. 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].

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