Synthesis of 16 alpha-[125I] iodo-5 alpha dihydrotestosterone and evaluation of its affinity for the androgen receptor.
Analogs of 5 alpha-dihydrotestosterone, halogenated at carbon 11, were synthesized as potential gamma-emitting ligands for the androgen receptor. These compounds, were chosen for synthesis because estradiol, similarly substituted, is strongly bound to the estrogen receptor, and both androgen and estrogen receptors have generally similar structural requirements for the D-ring. The 16 alpha-halogenated steroids, including 16 alpha-]125I] iodo-5 alpha-dihydrotestosterone were synthesized from 16 beta-bromo-5 alpha-dihydrotestosterone by halogen exchange. The cis-beta-bromohydrin substrate was synthesized from 5 alpha-androstane-3,17-dione by selective ketalization, dibromination at C-16 and stereoselective reduction, 16 alpha-iodo dihydrotestosterone was devoid of androgen activity in vivo at concentrations at which 5 alpha-dihydrotestosterone was fully stimulatory. The 16-alpha-iodo, 16 alpha-bromo, and 16-beta-bromo analogs were allowed to compete with [3H]-dihydrotestosterone for binding to the androgen receptor; the 16 alpha-iodo compound had a relative binding affinity 1/100th and both bromo compounds 1/30th that of dihydrotestosterone. In addition, no specific binding was detected when the 16 alpha-[125I]iodo analog was incubated with prostatic cytosol.
D000818:Animals; D001667:Binding, Competitive; D003600:Cytosol / Q000378:metabolism; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000378:metabolism; D007536:Isomerism; D008297:Male; D011467:Prostate / Q000378:metabolism; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D012741:Sexual Maturation
D011944:Receptors, Androgen; D011987:Receptors, Steroid; D013196:Dihydrotestosterone; C034896:16-iodostanolone