2-Methoxyestradiol and its analogs. Synthesis and structure—antiproliferative activity relationship

2-Methoxyestradiol is an estradiol metabolite capable of binding to the colchicine domain of the cell protein tubulin. The review systematizes the results of structure—activity studies on 2-methoxyestradiol analogs with various modifications of the A, B, and D rings and describes some synthetic approaches to such analogs. Ways of synthesis of metabolically stable 2-methoxyestradiol via modification of the 3- and 17-hydroxy groups, as well as by introduction of bulky substituents into the 17-position, are discussed. The design of 2-methoxyestradiol analogs lacking steroid fragment is also described.