Preparation of 17α-iodoethynylandrosta- And 17α-(2-iodoethenyl) androsta-4,6-dien-17β-ol-3-ones as active site-directed photoaffinity ligands for androgen-binding proteins

Article abstract of DOI:10.1016/0039-128X(92)90027-7

Unsaturated analogues of androst-4-en-17β-ol-3-one, each with a 17α-iodoethynyl or 17α-(2-iodoethenyl) substituent, were prepared, and their relative binding affinities (RB As) for androgen-binding protein (ABP) were compared with those of 5α-androstan-17β-ol-3-one, androst-4-en-17β-ol-3-one, androsta-4, 6-dien-17β-ol-3-one, and androsta-1,4,6-trien-17β-ol-3-one. These binding studies indicate that the iodine[¹²⁵I] analogues of 17α-iodoethynyl and 17α-[(E)-2-iodoethenyl] derivatives of androsta-4,6-dien-17β-ol-3-one and androsta-1,4,6-trien-17β-ol-3-one will have RBAs at least twice as great as that of 5α-androstan-17β-ol-3-one. They can be prepared from 17α-ethynylandrosta-4-en-17β-ol-3-one, the final synthetic step using N-[¹²⁵I]iodosuccinimide, and are potential radioiodinated, active site-directed photoaffinity ligands for ABP and testosterone-binding globulin.