Altrenogest
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. It is available for veterinary use in both Europe and the United States.
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 and the androgen receptor of a large selection of other progestogens as well as anabolic–androgenic steroids. The observed potency of altrenogest even exceeded that of metribolone, 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, whereas the AR/PR activational potency ratio of its 17α-deallylated AAS analogue trenbolone was, at 64, profoundly increased.
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 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. Altrenogest is the 17α-allylated derivative of the AAS trenbolone, which itself is the 9,11-didehydro analogue of the AAS nandrolone. 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-5,9-dien-17-one . Grignard reaction with allyl chloride gives PC14988798. Deprotection of the acetal using an aqueous solution of potassium bisulfate gives PC14988800. Oxidation with 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone completed the synthesis of altrenogest.