Anagestone acetate

Chemical compound

Pharmaceutical compound

Anagestone acetate

Clinical data
Trade names| Anatropin, Neo-Novum
Other names| ORF-1658; Anapregnone acetate; 3-Deketo-6α-methyl-17α-acetoxyprogesterone; 6α-Methyl-17α-hydroxypregn-4-en-20-one acetate
Routes of
administration| By mouth
Drug class| Progestogen; Progestin; Progestogen ester
Identifiers

IUPAC name

* [(6S,8R,9S,10R,13S,14S,17R)-17-acetyl-6,10,13-trimethyl-1,2,3,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-yl] acetate

CAS Number|

* 3137-73-3

PubChem CID|

* 252301

ChemSpider|

* 221058

UNII|

* GNT396G9QT

KEGG|

* D02932

ChEBI|

* CHEBI:135575

CompTox Dashboard (EPA)|

* DTXSID50953411

ECHA InfoCard| 100.019.578
Chemical and physical data
Formula| C24H36O3
Molar mass| 372.549 g·mol−1
3D model (JSmol)|

* Interactive image

SMILES

* C[C@H]1C[C@@H]2[C@H](CC[C@]3([C@H]2CC[C@@]3(C(=O)C)OC(=O)C)C)[C@@]4(C1=CCCC4)C

InChI

* InChI=1S/C24H36O3/c1-15-14-18-20(22(4)11-7-6-8-19(15)22)9-12-23(5)21(18)10-13-24(23,16(2)25)27-17(3)26/h8,15,18,20-21H,6-7,9-14H2,1-5H3/t15-,18+,20-,21-,22-,23-,24-/m0/s1

* Key:KDLNOQQQEBKBQM-DICPTYMLSA-N

Anagestone acetate, sold under the brand names Anatropin and Neo-Novum, is a progestin medication which was withdrawn from medical use due to carcinogenicity observed in animal studies.[1][2][3]

## Medical uses

[edit]

Anagestone acetate was used in combination with the estrogen mestranol as a combined birth control pill.[4][5]

## Pharmacology

[edit]

Based on its chemical structure, namely the lack of a C3 ketone, it is probable that anagestone acetate is a prodrug of medroxyprogesterone acetate (the 3-keto analogue).[6][7]

## Chemistry

[edit]

See also: List of progestogens, Progestogen ester, and List of progestogen esters

Anagestone acetate, also known as 3-deketo-6α-methyl-17α-acetoxyprogesterone or as 6α-methyl-17α-acetoxypregn-4-en-20-one, is a synthetic pregnane steroid and a derivative of progesterone and 17α-hydroxyprogesterone.[1] It is the C17α acetate ester of anagestone, which, in contrast to anagestone acetate, was never marketed.[1] Anagestone acetate is closely related structurally to medroxyprogesterone acetate (6α-methyl-17α-acetoxyprogesterone).[1]

## History

[edit]

Anagestone acetate was introduced in combination with mestranol as a birth control pill in 1968 by Ortho Pharmaceutical.[4][5] It was withdrawn in 1969.[5][8]

In 1969, along with a variety of other progestogens including progesterone, chlormadinone acetate, megestrol acetate, medroxyprogesterone acetate, ethynerone, and chloroethynyl norgestrel, anagestone acetate was found to induce the development of mammary gland tumors in Beagle dogs after extensive treatment (2–7 years) with very high doses (10–25 times the recommended human dose), though notably not with 1–2 times the human dosage.[5][9][8] In contrast, the non-halogenated 19-nortestosterone derivatives norgestrel, norethisterone, noretynodrel, and etynodiol diacetate were not found to produce such nodules.[8] Because of these findings, anagestone acetate was voluntarily withdrawn from the market by the manufacturer in 1969.[5][8][10] The findings also led to the virtual disappearance of most 17α-hydroxyprogesterone derivatives as hormonal contraceptives from the market (though medroxyprogesterone acetate, cyproterone acetate, and chlormadinone acetate have continued to be used).[5][9] According to Hughes et al., "It is still doubtful how much relevance these findings have for humans as the dog mammary gland seems to be the only one which can be directly maintained by progestogens."[8][11] Subsequent research revealed species differences between dogs and humans and established that there is no similar risk in humans.[12]

## Society and culture

[edit]

### Generic names

[edit]

Anagestone acetate is the generic name of the drug and its USANTooltip United States Adopted Name.[1] It is also known by its developmental code name ORF-1658.[1]

### Brand names

[edit]

Anagestone acetate was marketed under the brand names Anatropin and Neo-Novum, the latter in combination with the estrogen mestranol.[1]

### Availability

[edit]

Anagestone acetate was withdrawn from the market and is no longer available.[5][8][10]

## See also

[edit]

* Acetomepregenol

## References

[edit]

1. ^ a b c d e f g Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 85–. ISBN 978-1-4757-2085-3.
2. ^ William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 322–. ISBN 978-0-8155-1856-3.
3. ^ IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (1987). IV. OESTROGEN-PROGESTIN COMBINATIONS. International Agency for Research on Cancer. Retrieved 24 June 2022.
4. ^ a b Schreiner WE (6 December 2012). "The Ovary". In Labhart A (ed.). Clinical Endocrinology: Theory and Practice. Springer Science & Business Media. pp. 571–. ISBN 978-3-642-96158-8.
5. ^ a b c d e f g Streffer C, Bolt H, Follesdal D, Hall P, Hengstler JG, Jacob P, et al. (11 November 2013). "Interspecies Extrapolation". Low Dose Exposures in the Environment: Dose-Effect Relations and Risk Evaluation. Springer Science & Business Media. pp. 135–. ISBN 978-3-662-08422-9.
6. ^ Fraser IS (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."
7. ^ 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"1–2&rft.pages=39-47&rft.date=2008-05&rft_id=https://api.semanticscholar.org/CorpusID:5612000#id-name=S2CID&rft_id=info:pmid/18395441&rft_id=info:doi/10.1016/j.jsbmb.2007.10.008&rft.aulast=McRobb&rft.aufirst=L&rft.au=Handelsman,+DJ&rft.au=Kazlauskas,+R&rft.au=Wilkinson,+S&rft.au=McLeod,+MD&rft.au=Heather,+AK&rfr_id=info:sid/en.wikipedia.org:Anagestone+acetate" class="Z3988">
8. ^ a b c d e f Casey HW, Giles RC, Kwapien RP (1979). "Mammary Neoplasia in Animals: Pathologic Aspects and the Effects of Contraceptive Steroids". Carcinogenic Hormones. Vol. 66\. pp. 129–160 (149). doi:10.1007/978-3-642-81267-5_4. ISBN 978-3-540-08995-7. PMID 107546. `{{cite book}}`: `|journal=` ignored (help)
9. ^ a b Diczfalusy E (July 1979). "Gregory Pincus and steroidal contraception: a new departure in the history of mankind". Journal of Steroid Biochemistry. 11 (1A): 3–11\. doi:10.1016/0022-4731(79)90271-1. PMID 385985.
10. ^ a b Consolidated List of Products Whose Consumption And/or Sale Have Been Banned, Withdrawn, Severely Restricted Or Not Approved by Governments. United Nations Publications. 1983. pp. 25–. ISBN 978-92-1-130230-1.
11. ^ Gräf KJ, Brotherton J, Neumann F (27 November 2013). "The Clinical Uses of Antiandrogens". In Hughes A, Hasan SH, Oertel GW, Voss HE, Bahner F, Neumann F, et al. (eds.). Androgens II and Antiandrogens / Androgene II und Antiandrogene. Springer Science & Business Media. pp. 531–. ISBN 978-3-642-80859-3.
12. ^ Runnebaum BC, Rabe T, Kiesel L (6 December 2012). "Development of Progestogens". Female Contraception: Update and Trends. Springer Science & Business Media. pp. 134–135\. ISBN 978-3-642-73790-9.

* v
* t
* e

Progestogens and antiprogestogens

Progestogens
(and progestins)|

| PRTooltip Progesterone receptor agonists|

* Progesterone derivatives: Progesterone
* Quingestrone

* Retroprogesterone derivatives: Dydrogesterone
* Trengestone

* 17α-Hydroxyprogesterone (and closely related) derivatives: 17α-Hydroxylated: Acetomepregenol (mepregenol diacetate)
* Algestone acetophenide (dihydroxyprogesterone acetophenide)
* Anagestone acetate
* Chlormadinone acetate
* Chlormethenmadinone acetate
* Cyproterone acetate
* Delmadinone acetate
* Flugestone acetate (flurogestone acetate)
* Flumedroxone acetate
* Hydroxyprogesterone acetate
* Hydroxyprogesterone caproate
* Hydroxyprogesterone heptanoate
* Medroxyprogesterone acetate#
* Megestrol acetate
* Melengestrol acetate
* Methenmadinone acetate
* Osaterone acetate
* Pentagestrone acetate
* Proligestone; 17α-Methylated: Medrogestone; Others: Haloprogesterone

* 19-Norprogesterone derivatives: 17α-Hydroxylated: Gestonorone caproate (gestronol hexanoate)
* Nomegestrol acetate
* Norgestomet
* Segesterone acetate (nestorone, elcometrine); 17α-Methylated: Demegestone
* Promegestone
* Trimegestone

* Testosterone derivatives: Estranes: Danazol
* Dimethisterone
* Ethisterone

* 19-Nortestosterone derivatives: Estranes: Allylestrenol
* Altrenogest
* Dienogest
* Etynodiol diacetate
* Lynestrenol
* Norethisterone (norethindrone)#
* Norethisterone acetate
* Norethisterone enanthate
* Noretynodrel
* Norgesterone
* Norgestrienone
* Normethandrone (methylestrenolone)
* Norvinisterone
* Oxendolone
* Quingestanol acetate
* Tibolone; Gonanes: Desogestrel
* Etonogestrel
* Gestodene
* Gestrinone
* Levonorgestrel#
* Norelgestromin
* Norgestimate
* Norgestrel

* Spirolactone derivatives: Drospirenone

* Others: Anabolic–androgenic steroids (e.g., nandrolone and esters, trenbolone and esters, ethylestrenol, norethandrolone, others)

|

Antiprogestogens|

| SPRMsTooltip Selective progesterone receptor modulators|

* Telapristone§
* Ulipristal acetate

|

PRTooltip Progesterone receptor antagonists|

* Aglepristone
* Mifepristone

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

See also
Progesterone receptor modulators
Androgens and antiandrogens
Estrogens and antiestrogens
List of progestogens

* v
* t
* e

Progesterone receptor modulators

PRTooltip Progesterone receptor|

| Agonists|

* Progesterone derivatives: 3β-Dihydroprogesterone
* 5α-Dihydroprogesterone
* 6α-Methylprogesterone
* 9α-Bromo-11-ketoprogesterone
* 11-Dehydroprogesterone
* 11-Deoxycorticosterone
* 16α-Hydroxyprogesterone
* 17α-Methyl-11-deoxycorticosterone acetate
* 20α-Dihydroprogesterone
* 20β-Dihydroprogesterone
* Dimepregnen
* Diosgenin
* P1-185
* Progesterone
* Progesterone 3-acetyl enol ether
* Quingestrone

* Retroprogesterone derivatives: 20α-Dihydrodydrogesterone
* 20α-Dihydrotrengestone
* DU-41164
* DU-41165
* Dydrogesterone
* Retroprogesterone
* Ro 6-3129
* Trengestone

* 17α-Substituted progesterone derivatives: 6α-Methyl-17α-bromoprogesterone
* 15β-Hydroxycyproterone acetate
* 16-Methylene-17α-hydroxyprogesterone acetate
* 17α-Bromoprogesterone
* 17α-Hydroxyprogesterone (hydroxyprogesterone)
* 17α-Methylprogesterone
* Acetomepregenol (mepregenol diacetate)
* Algestone
* Algestone acetonide
* Algestone acetophenide
* Anagestone
* Anagestone acetate
* Bromethenmadinone
* Bromethenmadinone acetate
* Butagest (buterol)
* Chlormadinone
* Chlormadinone acetate
* Chlormadinone caproate
* Chlormethenmadinone
* Chlormethenmadinone acetate
* Cismadinone
* Cismadinone acetate
* Clogestone
* Clogestone acetate
* Clomegestone
* Clomegestone acetate
* Cymegesolate
* Cyproterone acetate
* Delmadinone
* Delmadinone acetate
* Edogestrone
* Flugestone
* Flugestone acetate
* Fluorometholone
* Fluorometholone acetate
* Flumedroxone
* Flumedroxone acetate
* Fluoromedroxyprogesterone acetate
* Gestaclone
* Gestobutanoyl
* Haloprogesterone
* Hydromadinone
* Hydromadinone acetate
* Hydroxyprogesterone acetate
* Hydroxyprogesterone caproate (hydroxyprogesterone hexanoate)
* Hydroxyprogesterone heptanoate (hydroxyprogesterone enanthate)
* Hydroxyprogesterone heptanoate benzilic acid hydrazone
* Mecigestone (pentarane B)
* Medrogestone
* Medroxyprogesterone
* Medroxyprogesterone acetate
* Medroxyprogesterone caproate
* Megestrol
* Megestrol acetate
* Megestrol caproate
* Melengestrol
* Melengestrol acetate
* Methenmadinone
* Methenmadinone acetate
* Methenmadinone caproate
* Mometasone
* Mometasone furoate
* Osaterone
* Osaterone acetate
* Pentagestrone
* Pentagestrone acetate
* Pentarane A
* Proligestone
* Triamcinolone acetonide

* 19-Norprogesterone derivatives: 17α-Methyl-19-norprogesterone
* 18-Methylsegesterone acetate
* 19-Norprogesterone
* Amadinone
* Amadinone acetate
* Demegestone
* Fluoro ethyl norprogesterone
* Fluoro furanyl norprogesterone
* Gestadienol
* Gestadienol acetate
* Gestonorone acetate (gestronol acetate)
* Gestonorone caproate (gestronol hexanoate)
* Gestronol (gestonorone)
* Nomegestrol
* Nomegestrol acetate
* Norgestomet
* ORG-2058
* Oxogestone
* Oxogestone phenpropionate (xinogestone)
* Promegestone
* Segesterone
* Segesterone acetate (nestorone)
* Trimegestone

* Testosterone derivatives: Progestins: 6,6-Difluoronorethisterone
* 6,6-Difluoronorethisterone acetate
* 17α-Allyl-19-nortestosterone
* Allylestrenol
* Altrenogest
* Chloroethynylnorgestrel
* Cingestol
* Danazol
* Desogestrel
* Dienogest
* Ethinylandrostenediol
* Ethandrostate
* Ethisterone
* Ethynerone
* Etonogestrel
* Etynodiol
* Etynodiol diacetate
* Gestodene
* Gestrinone
* Levonorgestrel
* Levonorgestrel esters (e.g., levonorgestrel butanoate)
* Lynestrenol
* Lynestrenol phenylpropionate
* Metynodiol
* Metynodiol diacetate
* Norelgestromin
* Norethisterone (norethindrone)
* Norethisterone esters (e.g., norethisterone acetate, norethisterone enanthate)
* Noretynodrel
* Norgesterone
* Norgestimate
* Norgestrel
* Norgestrienone
* Norvinisterone
* Oxendolone
* Quingestanol
* Quingestanol acetate
* Tibolone
* Tigestol
* Tosagestin; Anabolic–androgenic steroids: 11β-Methyl-19-nortestosterone
* 11β-Methyl-19-nortestosterone dodecylcarbonate
* 19-Nor-5-androstenediol
* 19-Nor-5-androstenedione
* 19-Nordehydroepiandrosterone
* Bolandiol
* Bolandiol dipropionate
* Bolandione
* Dimethisterone
* Dienedione
* Dienolone
* Dimethandrolone
* Dimethandrolone buciclate
* Dimethandrolone dodecylcarbonate
* Dimethandrolone undecanoate
* Dimethyldienolone
* Dimethyltrienolone
* Ethyldienolone
* Ethylestrenol (ethylnandrol)
* Methyldienolone
* Metribolone (R-1881)
* Methoxydienone (methoxygonadiene)
* Mibolerone
* Nandrolone
* Nandrolone esters (e.g., nandrolone decanoate, nandrolone phenylpropionate)
* Norethandrolone
* Normethandrone (methylestrenolone, normethandrolone, normethisterone)
* RU-2309
* Tetrahydrogestrinone
* Trenbolone (trienolone)
* Trenbolone esters (e.g., trenbolone acetate, trenbolone enanthate)
* Trendione
* Trestolone
* Trestolone acetate

* Spirolactone derivatives: Canrenoic acid
* Canrenone
* Drospirenone
* Mespirenone
* Potassium canrenoate
* Prorenone
* SC-5233 (spirolactone)
* SC-8109
* Spironolactone
* Spirorenone

* Nonsteroidal: 3,8-Dihydrodiligustilide
* LG-2527
* LG-100128
* Riligustilide
* RWJ-26819
* RWJ-49853
* RWJ-60130
* Tanaproget
* ZM-182345

* Unknown: ORG-47241
* ORG-201745

|

Mixed
(SPRMsTooltip Selective progesterone receptor modulators)|

* Steroidal: Dihydroethisterone
* 5α-Dihydrolevonorgestrel
* 5α-Dihydronorethisterone
* Asoprisnil
* Asoprisnil ecamate
* Guggulsterone
* J1042
* LG-120838
* Metapristone (RU-42633)
* Mifepristone (RU-486)
* ORF-9371
* ORF-9326
* ORG-31710
* ORG-33628
* RMI-12936
* Telapristone
* Ulipristal acetate
* Vilaprisan
* ZK-137316

* Nonsteroidal: Apigenin
* Kaempferol
* LG-120920
* Naringenin
* PRA-910
* Syringic acid

Antagonists|

* Steroidal: Aglepristone
* Lilopristone
* Lonaprisan
* Onapristone
* ORG-31710
* ORG-31806
* ORG-33628
* RTI 3021–022
* Toripristone
* Zanoterone

* Nonsteroidal: Darolutamide
* LG-001447
* LG-100127
* LG-100128
* LG-120830
* LG-121046
* Valproic acid
* ZM-150271
* ZM-172406

mPRTooltip Membrane progesterone receptor
(PAQRTooltip Progestin and adipoQ receptor)|

| Agonists|

* 5α-Dihydroprogesterone
* 5β-Dihydroprogesterone
* 11-Deoxycortisone (21-hydroxyprogesterone)
* 11-Deoxycortisol (17α,21-dihydroxyprogesterone)
* 17α-Hydroxyprogesterone
* Allopregnanolone
* Mifepristone
* Pregnenolone
* Progesterone

|

Antagonists|

* Mifepristone

See also
Receptor/signaling modulators
Progestogens and antiprogestogens
Androgen receptor modulators
Estrogen receptor modulators
List of progestogens
*[CID]: Compound ID
*[EPA]: U.S. Environmental Protection Agency
*[USAN]: United States Adopted Name
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[PR]: Progesterone receptor
*[SPRMs]: Selective progesterone receptor modulators
*[mPR]: Membrane progesterone receptor
*[PAQR]: Progestin and adipoQ receptor