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Synthesis and Pharmacological Evaluation of Dimeric Follicle‐Stimulating Hormone Receptor Antagonists
Author(s) -
Bonger Kimberly M.,
Hoogendoorn Sascha,
van Koppen Chris J.,
Timmers Cornelis M.,
Overkleeft Herman S.,
van der Marel Gijsbert A.
Publication year - 2009
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200900344
Subject(s) - follicle stimulating hormone receptor , hormone receptor , follicle stimulating hormone , receptor , pharmacology , chemistry , hormone , medicine , endocrinology , biology , biochemistry , luteinizing hormone , cancer , breast cancer
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.