Altrenogest

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). The observed potency of altrenogest even exceeded that of metribolone (methyltrienolone, R-1881), which was the second most potent compound. 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.

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

According to its manufacturer Roussel Uclaf, altrenogest has weak anabolic and androgenic activity equivalent to 1/20th of that of testosterone. However, no significant androgenic effects have been observed in young stallions or mature mares, 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. On the other hand, minor potential anabolic/androgenic effects have been suggested for altrenogest in pigs.

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. It is one of only two marketed progestins that possesses a 17α-allyl group, the other being allylestrenol. 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). 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). Altrenogest is also closely related to norgestrienone.

Synthesis

The chemical synthesis has been described: Prior art: 20th century methods:

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.

Society and culture

Generic names

Altrenogest is the generic name of the drug and its , , and , while altrénogest is its .

Brand names

Altrenogest is marketed under the brand names Regumate and Matrix among others.

References

References

1. (24 August 2005). "Wildlife Contraception: Issues, Methods, and Applications". JHU Press.
2. (3 August 2022). "Health product highlights 2021: Annexes of products approved in 2021".
3. (14 November 2014). "The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies". Springer.
4. (January 2000). "Index Nominum 2000: International Drug Directory". Taylor & Francis.
5. "Altrenogest". Drugs.com.
6. (13 May 2013). "Veterinary Pharmacology and Therapeutics". John Wiley & Sons.
7. (1990). "Medicinal chemistry of steroids". Elsevier Science Limited.
8. (1 April 2010). "Control of Pig Reproduction VIII". Nottingham University Press.
9. (May 2008). "Structure-activity relationships of synthetic progestins in a yeast-based in vitro androgen bioassay". The Journal of Steroid Biochemistry and Molecular Biology.
10. (February 1988). "Growth, carcass traits, boar odor and testicular and endocrine functions of male pigs fed a progestogen, altrenogest". Journal of Animal Science.
11. (4 October 2013). "Using Science to Improve the BLM Wild Horse and Burro Program: A Way Forward". National Academies Press.
12. Liu Xirong, et al. CN117106002 (2023 to Hunan Xinhexin Biological Medicine Co ltd).
13. 高伟, et al. CN106946961 (2017 to Prompt Bio Tech Ltd Of Xiamen Allred).
14. Qian Xingyu, et al. CN106810584 (2017 to Ningbo Second Hormone Factory).
15. DE1618810 idem Daniel Bertin, Andre Pierdet, US3484462 (1969 to Roussel Uclaf).
16. , FR5183M (1967-06-19).
17. (5 July 2011). "Equine Reproduction". John Wiley & Sons.