title: Synthesis and pharmacological evaluation of dimeric follicle-stimulating hormone receptor antagonists.
abstract: A series of homo- and heterodimeric compounds encompassing the follicle-stimulating hormone receptor (FSHR) antagonist (R)-1 and its inactive conformer (S)-1 connected through ethylene glycol spacers of various lengths is described. Evaluation of these compounds reveals that dimeric compounds, with a spacer of sufficient length, bearing two active copies of the antagonist are more potent relative to dimeric compounds in which one of the active pharmacophores is replaced by an inactive conformer. Interestingly, the opposite trend is observed if a short spacer is used, indicating that these compounds may be valuable tools to study FSHR dimerization in greater detail.
authors.affiliation: Leiden Institute of Chemistry, Department of Bioorganic Synthesis, Gorlaeus Laboratories, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Bonger
authors.forename: Sascha
authors.initials: S
authors.lastname: Hoogendoorn
authors.forename: Chris J
authors.initials: CJ
authors.lastname: van Koppen
authors.forename: Cornelis M
authors.initials: CM
authors.lastname: Timmers
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
authors.forename: Gijsbert A
authors.initials: GA
authors.lastname: van der Marel
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D019281:Dimerization; D008024:Ligands; D015394:Molecular Structure; D011962:Receptors, FSH / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D011962:Receptors, FSH