2. Academic Validation
  3. Design and Synthesis of 4-(4-Benzoylaminophenoxy)phenol Derivatives As Androgen Receptor Antagonists

Design and Synthesis of 4-(4-Benzoylaminophenoxy)phenol Derivatives As Androgen Receptor Antagonists

  • ACS Med Chem Lett. 2013 Aug 19;4(10):937-41. doi: 10.1021/ml4001744.
Ayumi Yamada 1,  Shinya Fujii 1,  Shuichi Mori 1,  Hiroyuki Kagechika 1
Affiliations

Affiliation

  • 1 Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University , 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
PMID: 24900588 DOI: 10.1021/ml4001744
Abstract

We report the design and synthesis of novel 4-(4-benzoylaminophenoxy)phenol derivatives that bind to the Androgen Receptor (AR) ligand-binding domain and exhibit potent androgen-antagonistic activity. Compound 22 is one of the most potent of these derivatives, inhibiting the dihydrotestosterone-promoted growth of SC-3 cell line bearing wild-type AR (IC50 0.75 μM), LNCaP cell line bearing T877A-mutated AR (IC50 0.043 μM), and 22Rv1 cell line bearing H874Y-mutated AR (IC50 0.22 μM). Structure-activity relationship studies confirmed that the pharmacophore of these novel AR antagonists is distinct from the nitro- or cyano-substituted anilide substructure of Other nonsteroidal AR antagonists. This novel pharmacophore is expected to provide a basis for designing new antiprostate Cancer agents.

Keywords

4-(4-benzoylaminophenoxy)phenol; AR antagonist; Androgen receptor (AR); pharmacophore; prostate cancer.

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