Molecular identification of steroid analogs with dissociated antiprogestin activities.

ABSTRACT

Antiprogestins of the 11 beta-aryl-substituted 19-norsteroid family are effectively used in inhibiting nidation and in terminating pregnancies. They are potentially useful in the treatment of progesterone-related diseases such as meningiomas and endometriosis and in inhibiting the growth of mammary tumors. However their long-term use is limited because of their inherent antiglucocorticoid activity. Here we have used molecular biological techniques to examine the antiglucocorticoid activity of a series of antiprogestins. The compounds we have analyzed contain different substituents at the C-17 position and a change from the trans to cis configuration of the C-D steroid rings. Our results show that minor changes at the C-17 position but not in the configuration of the C and D rings produced antiprogestins with reduced antiglucocorticoid activity. Thus only subtle changes in the structure of classical antiprogestins are needed for the reduction of their antiglucocorticoid activities.