(±)-Yuehchukene (YCK) is a novel bis-indole alkaloid with potent anti-implantation activity in rats. The present paper reports the activity of YCK derivatives by substitution on the parent compound. Substitutions on the indole nitrogens or on 2- and 5′-positions of the indole moiety abolished activity. N-1′-methylation of the free indole only permitted a 30% residual activity. Saturation of the C9C10 cyclohexenyl double bond did not affect activity at all. Hydroxylation, whether on the C9C10 double bond, or at C2 or C5, rendered the hydroxylated derivatives inactive. This suggests that the active metabolite in anti-implantation was probably not a hydroxylated derivative carrying estrogenic activity. © 1991.