2,17α-dimethyl-17β-hydroxy-5α-androst-2-ene or 2,17a-dimethyl-17b-hydroxy-5a-androst-2-ene

Posted by BPP on 8th Apr 2014

Nomenclature:
2,17α-dimethyl-17β-hydroxy-5α-androst-2-ene or
2,17a-dimethyl-17b-hydroxy-5a-androst-2-ene

Name:
There’s no generally-accepted trivial name for this compound. It’s structurally very closely related to desoxymethyltestosterone (“pheraplex”), which was named methylandrostenol when first discovered as a doping agent. Methylandrostenol was subsequently shortened for convenience to the acronym ‘madol’. [1] By that rationale, since this compound has an additional methyl group, the trivial name dimethandrostenol would seem to fit. Desoxymethasterone would be an alternative way of describing it.

History:
Experiments at Syntex in the early 1960s established that steroids that lacked a C-3 oxygen atom, but had a double bond somewhere in the A-ring (particularly C2-C3), could still be effective anabolic agents; the oral activity of desoxymethyltestosterone in particular was noted. [2]
Additional research by the same team demonstrated that substitution with a methyl group to C2 unsaturated compounds increased oral activity further.

J. Med. Chem. 1963 Mar 1;6(2):162–6. [3]
Both this compound (the 2-methyl), and the 2-methylene analogue were found to have a strong anabolic effect and a good dissociation of anabolic and androgenic effects in preliminary testing. [3][4]

J. Med. Chem. 1962 Mar 1,5(2),406–8J. Med. Chem. 1962 Mar 1;5(2):406–8. [4]
Like many other drugs such as methasterone and desoxymethyltestosterone, dimethandrostenol was never commercialized by Syntex. In 2013 it was released on to the dietary supplement market as Mithras from Iron Legion.

Anabolic Androgenic Ratio:
Preliminary testing indicated that it was very strong, with an anabolic to androgenic ratio of around 1000:200. The 2-methylene analogue was markedly weaker – though still potent. [3]

2-methylandrostenes table oral activityJ. Med. Chem. 1963 Mar 1;6(2):162–6. [3]
When subjected to further testing by researchers from the same lab, levator ani/ventral prostate/seminal vesicle figures of 1040:320:97 were confirmed. [5]

“The 2,17a-dimethyl derivative, a 3-deoxy steroid, had the remarkable activity of 1,040% on the levator ani, 97% on the ventral prostate, and 320% on the seminal vesicle.” [5]

delta 2 steroids by gavageEndocrinology. 1963 Feb 1;72(2):259–66 [5]
These results were summarized in Julius Vida’s 1969 work Androgens and Anabolic Agents.

217a-dimethyl-17b-hydroxy-5a-androst-2-ene-VidaAndrogens and Anabolic Agents. 1969. Academic Press. p. 215 [6]

Relationship to other compounds:

steroid family
The “family” of structurally-related compounds illustrated above are all powerful anabolic agents (as can be seen by the anabolic:androgenic ratios quoted below).
Table 1: Anabolic/Androgenic Ratios of a series of A-ring modified steroids Compound Anabolic Androgenic Lab
LA VP SV
Desoxymethyltestosterone 437 119 218 Syntex [7]
Dimethandrostenol 1040 97 320 Syntex [5]
Methasterone 800 20 20 Syntex [8][9]
Methylstenbolone 660 90 170 Searle & Co. [10]
Methyl-1-testosterone 910 220 180 Searle & Co. [10]

LA = Levator ani (demonstrates anabolic potency). VP = Ventral prostate, and SV = Seminal vesicles (markers of androgenic potency)

Structure and Function:
Dimethandrostenol can be considered to be like methasterone (superdrol) with an additional double bond, or like desoxymethyltestosterone (phera-plex) with an additional 2-methyl group.
The presence of the adjacent double-bond causes the C-2 methyl group of dimethandrostenol to be planar (as with stenbolone and methyl stenbolone), unlike 2-methyl groups on saturated A-rings (like masteron and superdrol), which have to be in the alpha or beta position (alpha, in those examples).

Metabolism:
Dimethandrostenol cannot aromatize to form estrogenic metabolites, as it has no C4-5 double bond (it is ’5α-reduced’). For the same reason, it is not a substrate for (cannot be transformed by) the enzyme 5α-reductase (the enzyme that catalyzes the reaction that turns testosterone to DHT).
Potential metabolic transformations could include the reduction of the delta-2 double bond, formation of a 2-methylene metabolite, and various hydroxylation reactions. In desoxymethyltestosterone the double bond is fairly readily reduced; in dimethandrostenol it’s likely that the adjacent methyl group increases resistance to reduction of the double bond.
The toxicity of oral steroids appears to be closely related to both potency and resistance to metabolism. Given that this compound is extremely potent, and is likely to be fairly resistant to metabolism, it’s fair to assume it has a toxicity profile similar to other drugs of its class (i.e. those already mentioned).