Quantitative relations between steroid structure and binding to putative progesterone receptors

Abstract

Relationships between the chemical structure of androst-4-en-3-one derivatives and their affinity for putative progesterone receptors were described for the sheep, rabbit, guinea pig and human. The binding affinity for 55 derivatives was expressed by the equation log relative binding affinity (rabbit receptor) = 1.79 + 0.18 (.+-. 0.11 .pi.a + 1.45 (.+-. 0.21).pi.b + 0.010 (.+-. 0.002) (surface area in hydrophobic pockets) -0.012 (.+-. 0.003) (surface area out of hydrophobic pockets) =0.99 (.+-. 0.21) MK -0.33 (.+-. 0.08) (conformational changes). For this equation, r = 0.88. The equation successfully predicted the affinities of other compounds in the literature. The importance of the surface area terms was discussed.