Novel androgen receptor full antagonists: Design, synthesis, and a docking study of glycerol and aminoglycerol derivatives that contain p-carborane cages

Publication date: Available online 7 June 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Asako Kaise, Kiminori Ohta, Shinya Fujii, Akifumi Oda, Tokuhito Goto, Yasuyuki Endo
Based on the co-crystal structure of bicalutamide with a T877A-mutated androgen receptor (AR), glycerol and aminoglycerol derivatives were designed and synthesized as a novel type of carborane-containing AR modulators. The (R)-isomer of 6c, whose chirality is derived from the glycerol group, showed 20 times more potent cell inhibitory activity against LNCaP cell lines expressing T877A-mutated AR than the corresponding (S)-isomer. Docking studies of both isomers with AR suggested that (R)-6c is in closer spatial proximity to helix-12 of the AR than (S)-6c, which is the most important common motif in the secondary structure of AR for the expression of antagonistic activity.

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