title: Antiandrogenic steroidal sulfonyl heterocycles. Utility of electrostatic complementarity in defining bioisosteric sulfonyl heterocycles.
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.
authors.affiliation: Department of Medicinal Chemistry, Sterling Winthrop Pharmaceuticals Research Division, Rensselaer, New York 12144.
authors.forename: J P
authors.initials: JP
authors.lastname: Mallamo
authors.forename: G M
authors.initials: GM
authors.lastname: Pilling
authors.forename: J R
authors.initials: JR
authors.lastname: Wetzel
authors.forename: P J
authors.initials: PJ
authors.lastname: Kowalczyk
authors.forename: M R
authors.initials: MR
authors.lastname: Bell
authors.forename: R K
authors.initials: RK
authors.lastname: Kullnig
authors.forename: F H
authors.initials: FH
authors.lastname: Batzold
authors.forename: P E
authors.initials: PE
authors.lastname: Juniewicz
authors.forename: R C
authors.initials: RC
authors.lastname: Winneker
authors.forename: H R
authors.initials: HR
authors.lastname: Luss
mesh_terms: D000726:Androgen Antagonists / Q000737:chemistry* / Q000145:classification; D059002:Androgen Receptor Antagonists; D004563:Electrochemistry; D006571:Heterocyclic Compounds / Q000737:chemistry*; D011944:Receptors, Androgen / Q000378:metabolism; D013379:Substrate Specificity; D014961:X-Ray Diffraction
chemical_list: D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D006571:Heterocyclic Compounds; D011944:Receptors, Androgen