2. Academic Validation
  3. N-aryl-oxazolidin-2-imine muscle selective androgen receptor modulators enhance potency through pharmacophore reorientation

N-aryl-oxazolidin-2-imine muscle selective androgen receptor modulators enhance potency through pharmacophore reorientation

  • J Med Chem. 2009 May 14;52(9):2794-8. doi: 10.1021/jm801583j.
Alexandra A Nirschl 1,  Yan Zou,  Stanley R Krystek Jr,  James C Sutton,  Ligaya M Simpkins,  John A Lupisella,  Joyce E Kuhns,  Ramakrishna Seethala,  Rajasree Golla,  Paul G Sleph,  Blake C Beehler,  Gary J Grover,  Donald Egan,  Aberra Fura,  Viral P Vyas,  Yi-Xin Li,  John S Sack,  Kevin F Kish,  Yongmi An,  James A Bryson,  Jack Z Gougoutas,  John DiMarco,  Robert Zahler,  Jacek Ostrowski,  Lawrence G Hamann
Affiliations

Affiliation

  • 1 Discovery Chemistry, Analytical Research & Development, Bristol-Myers Squibb Research and Development, P.O. Box 5400, Princeton, New Jersey 08543-5400, USA.
PMID: 19351168 DOI: 10.1021/jm801583j
Abstract

A novel selective Androgen Receptor modulator (SARM) scaffold was discovered as a byproduct obtained during synthesis of our earlier series of imidazolidin-2-ones. The resulting oxazolidin-2-imines are among the most potent SARMs known, with many analogues exhibiting sub-nM in vitro potency in binding and functional assays. Despite the potential for hydrolytic instability at gut pH, compounds of the present class showed good oral bioavailability and were highly active in a standard rodent pharmacological model.

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