Altrenogest

Last updated
Altrenogest
Altrenogest.svg
Clinical data
Trade names Regumate, Matrix
Other namesAllyltrenbolone; Allyltrienolone; RU-2267; RH-2267; A-35957; A-41300; 17α-Allylestra-4,9,11-trien-17β-ol-3-one; 17α-Allyl-19-nor-δ9,11-testosterone
Routes of
administration 		By mouth [1]
Drug class Progestogen; Progestin
ATCvet code
Legal status
Legal status
Identifiers
  • (8S,13S,14S,17R)-17-Hydroxy-13-methyl-17-prop-2-enyl-1,2,6,7,8,14,15,16-octahydrocyclopenta[a]phenanthren-3-one
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.011.549 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C21H26O2
Molar mass 310.437 g·mol−1
3D model (JSmol)
  • C[C@]12C=CC3=C4CCC(=O)C=C4CC[C@H]3[C@@H]1CC[C@]2(CC=C)O
  • InChI=1S/C21H26O2/c1-3-10-21(23)12-9-19-18-6-4-14-13-15(22)5-7-16(14)17(18)8-11-20(19,21)2/h3,8,11,13,18-19,23H,1,4-7,9-10,12H2,2H3/t18-,19+,20+,21+/m1/s1
  • Key:VWAUPFMBXBWEQY-ANULTFPQSA-N

Altrenogest, sold under the brand names Swinemate and Altren manufactured by Aurora Pharmaceutical and Regumate manufactured by Merck, is a progestin of the 19-nortestosterone group which is widely used in veterinary medicine to suppress or synchronize estrus in horses and pigs. [3] [4] [5] [6] [7] It is available for veterinary use in both Europe (as Regumate) and the United States (as Matrix). [8]

Contents

Uses

Veterinary

Altrenogest is used in veterinary medicine.

Pharmacology

Pharmacodynamics

An in vitro yeast structure–activity relationships bioassay study found that altrenogest was the most potent agonist of both the progesterone receptor (PR) and the androgen receptor (AR) of a large selection of other progestogens as well as anabolic–androgenic steroids (AAS). [9] The observed potency of altrenogest even exceeded that of metribolone (methyltrienolone, R-1881), which was the second most potent compound. [9] In the study, it showed an EC50 of 0.64 nM for the AR and 688% of the relative activational potency of testosterone and an EC50 of 0.3 nM and 1,300% of the relative activational potency of progesterone, with an AR/PR activational potency ratio of 0.53. [9]

Although very potent in both activities in vitro, the AR/PR activational potency ratio of altrenogest was in the same range as that of other 19-nortestosterone progestins such as norethisterone, noretynodrel, norgestrel, and allylestrenol (ratio for all < 1.0), whereas the AR/PR activational potency ratio of its 17α-deallylated AAS analogue trenbolone was, at 64, profoundly increased (although the ratio of metribolone (the 17α-methylated variant of altrenogest), at 0.56, was almost the same as that of altrenogest). [9]

According to its manufacturer Roussel Uclaf, altrenogest has weak anabolic and androgenic activity equivalent to 1/20th of that of testosterone. [10] However, no significant androgenic effects have been observed in young stallions or mature mares, [11] and altrenogest has notably been used to maintain pregnancy in mares (similarly to the use of allylestrenol to maintain pregnancy in women) with no incidence of virilization or other abnormalities in filly offspring. [12] On the other hand, minor potential anabolic/androgenic effects have been suggested for altrenogest in pigs. [11]

Chemistry

Altrenogest, also known as 17α-allyl-19-nor-δ9,11-testosterone or as 17α-allylestra-4,9,11-trien-17β-ol-3-one, is a synthetic estrane steroid and derivative of 19-nortestosterone and 17α-allyltestosterone, or of 17α-allyl-19-nortestosterone. [3] [4] [7] It is one of only two marketed progestins that possesses a 17α-allyl group, the other being allylestrenol. [3] [4] Most other progestins possess a 17α-ethynyl group, while AAS, if they are 17α-substituted, are usually 17α-alkylated (with a methyl or ethyl group). [3] [4] Altrenogest is the 17α-allylated derivative of the AAS trenbolone (and hence can also be referred to as allyltrenbolone or allyltrienolone), which itself is the 9,11-didehydro analogue of the AAS nandrolone (19-nortestosterone). [3] [4] Altrenogest is also closely related to norgestrienone. [3] [4]

Synthesis

The chemical synthesis has been described: [13] Prior art: [14] [15] 20th century methods: [16] [17]

Altrenogest synthesis.svg

Dienedione is converted to it’s dimethylacetal to give 3,3-dimethoxyestra-5(10),9(11)-dien-17-one [10109-76-9] (1). Grignard reaction with allyl chloride [107-05-1] gives PC14988798 (2). Deprotection of the acetal using an aqueous solution of potassium bisulfate gives PC14988800 (3). Oxidation with 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone [84-58-2] completed the synthesis of altrenogest (4).

History

Altrenogest has been marketed as Regumate since the early 1980s. [11]

Society and culture

Generic names

Altrenogest is the generic name of the drug and its INN Tooltip International Nonproprietary Name, USAN Tooltip United States Adopted Name, and BAN Tooltip British Approved Name, while altrénogest is its DCF Tooltip Dénomination Commune Française. [3] [4] [5]

Brand names

Altrenogest is marketed under the brand names Regumate and Matrix among others. [3] [4] [5]

References

  1. ↑ Asa CS (24 August 2005). "Types of contraception: The Choices". In Asa CS, Porton IJ (eds.). Wildlife Contraception: Issues, Methods, and Applications. JHU Press. pp. 35–. ISBN   978-0-8018-8304-0.
  2. ↑ "Health product highlights 2021: Annexes of products approved in 2021". Health Canada . 3 August 2022. Retrieved 25 March 2024.
  3. 1 2 3 4 5 6 7 8 Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 35–. ISBN   978-1-4757-2085-3.
  4. 1 2 3 4 5 6 7 8 Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 33–. ISBN   978-3-88763-075-1.
  5. 1 2 3 "Altrenogest". Drugs.com. Archived from the original on 2017-12-01. Retrieved 2017-11-25.
  6. ↑ Reddy DS, Gadsby JE (13 May 2013). "Hormones Affecting Reproduction". In Riviere JE, Papich MG (eds.). Veterinary Pharmacology and Therapeutics. John Wiley & Sons. pp. 727–. ISBN   978-1-118-68590-7.
  7. 1 2 Zeelen FJ (1990). Medicinal chemistry of steroids. Elsevier Science Limited. pp. 108–109. ISBN   978-0-444-88727-6. Other examples are allylestrenol (42), a pro-drug converted to the 3-keto analogue (43), which is used in the treatment of threatened abortion [78,79] and altrenogest (44), used in sows and mares to suppress ovulation and estrus behaviour [80]. [...] Progestins with a 17a-allyl side chain: (42) allylestrenol, (43), (44) altrenogest.
  8. ↑ Rodriguez-Martinez H (1 April 2010). Control of Pig Reproduction VIII. Nottingham University Press. pp. 189–. ISBN   978-1-907284-53-3.
  9. 1 2 3 4 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.
  10. ↑ Kluber EF, Minton JE, Stevenson JS, Hunt MC, Davis DL, Hoagland TA, Nelssen JL (February 1988). "Growth, carcass traits, boar odor and testicular and endocrine functions of male pigs fed a progestogen, altrenogest". Journal of Animal Science. 66 (2): 470–478. doi:10.2527/jas1988.662470x. PMID   3131291.
  11. 1 2 3 McKinnon AO, Squires EL, Vaala WE, Varner DD (5 July 2011). Equine Reproduction. John Wiley & Sons. pp. 4462–. ISBN   978-0-470-96187-2.
  12. ↑ Committee to Review the Bureau of Land Management Wild Horse and Burro Management Program; Board on Agriculture and Natural Resources; Division on Earth and Life Studies; National Research Council (4 October 2013). Using Science to Improve the BLM Wild Horse and Burro Program: A Way Forward. National Academies Press. pp. 120–. ISBN   978-0-309-26494-5.
  13. ↑ Liu Xirong, et al. CN117106002 (2023 to Hunan Xinhexin Biological Medicine Co ltd).
  14. ↑ 高伟, et al. CN106946961 (2017 to Prompt Bio Tech Ltd Of Xiamen Allred).
  15. ↑ Qian Xingyu, et al. CN106810584 (2017 to Ningbo Second Hormone Factory).
  16. ↑ DE1618810 idem Daniel Bertin, Andre Pierdet, US3484462 (1969 to Roussel Uclaf).
  17. ↑ , FR5183M (1967-06-19).
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