Document Report Card

ID: ALA1126028

Journal: J Med Chem

Title: Antiandrogenic steroidal sulfonyl heterocycles. Utility of electrostatic complementarity in defining bioisosteric sulfonyl heterocycles.

Authors: Mallamo JP, Pilling GM, Wetzel JR, Kowalczyk PJ, Bell MR, Kullnig RK, Batzold FH, Juniewicz PE, Winneker RC, Luss HR.

Abstract: Complementarity of electrostatic potential surface maps was utilized in defining bioisosteric steroidal androgen receptor antagonists. Semiempirical and ab initio level calculations performed on a series of methanesulfonyl heterocycles indicated the requirement for a partial negative charge at the heteroatom attached to C-3 of the steroid nucleus to attain androgen receptor affinity. Synthesis and testing of six heterocycle A-ring-fused dihydroethisterone derivatives support this hypothesis, and we have identified two new androgen receptor antagonists of this class.

CiteXplore: 1588549

DOI: 10.1021/jm00088a001