Synthesis and biological activity of some ethers of testosterone. Implications concerning the biological activity of esters of testosterone.
The benzyl (2), allyl (4), propyl (10), 3-hydroxypropyl (12), 2,3-dihydroxypropyl (11), 4 pentenyl (7), and pentyl (8) ethers of testosterone were synthesized. Compounds 2, 4, 7, 8, 10, and 12 were found to be almost devoid of anabolic or androgenic activity in a modified Hershberger Assay, but 2,4,10, and 12 were found to be effective inhibitors of testosterone 5alpha-reductase from human skin. These findings suggest that esters of testosterone and of 19-nortestosterone must hydrolyze before interacting with the hormonal receptors, but that the esters may competitively compete with the parent alchohols for interaction with enzymes. The latter effect may shift the distribution of metabolites of the esters relative to the alchohols and thus influence the pharmacological effect of these compounds.
D000818:Animals; D004952:Esters; D004987:Ethers / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D008297:Male; D009132:Muscles / Q000187:drug effects; D009929:Organ Size; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D011467:Prostate / Q000187:drug effects; D051381:Rats; D012669:Seminal Vesicles / Q000187:drug effects; D012867:Skin / Q000201:enzymology; D013739:Testosterone / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology
D004952:Esters; D004987:Ethers; D013739:Testosterone; D010088:Oxidoreductases