Steroid Flexibility and Receptor Specificity.pdf
Thus, the 2-gem-dimethyl derivative of RU 1881, namely RU 2956, unlike the 6-gem-dimethyl derivative (RU 4743) competed only very slightly for androgen receptor binding; the 2- and especially 4-monomethyl derivatives (RU 2922 and RU 4089 respectively) were some- what more effective competitors both for binding to the androgen and progestin receptors, but nevertheless were weaker than the unsubstituted compound, RU 1881. On the other hand, both the corresponding A-nor and 2-0~0 derivatives were good competitors (Table 6). (c) They must put into play a total interaction energy (hydrogen bonds and hydrophobic vander Waals forces) comparable to that of the corresponding natural hormone. Thus. nortestosterone did not compete effectively for binding to the progestin receptor in the absence of a 17~~carbon substituent or of additional A9,ll double bonds (see Table 4).
There is some serious activity going on at the progestin, mineralcorticoid, and glucocorticoid receptors. I wonder if any of these modifications would reduce the hepatotoxicity of methyl trenbolone?