2. Academic Validation
  3. Synthesis and SAR study of novel pseudo-steroids as potent and selective progesterone receptor antagonists

Synthesis and SAR study of novel pseudo-steroids as potent and selective progesterone receptor antagonists

  • Bioorg Med Chem Lett. 2009 Jul 15;19(14):3977-80. doi: 10.1016/j.bmcl.2009.01.095.
Nareshkumar Jain 1,  George Allan,  Olivia Linton,  Pamela Tannenbaum,  Xin Chen,  Jun Xu,  Peifang Zhu,  Joseph Gunnet,  Keith Demarest,  Scott Lundeen,  William Murray,  Zhihua Sui
Affiliations

Affiliation

  • 1 Johnson and Johnson Pharmaceutical Research and Development, Medicinal Chemistry, LLC, Exton, PA 19341, USA. drnfjain@gmail.com
PMID: 19217285 DOI: 10.1016/j.bmcl.2009.01.095
Abstract

Synthesis of novel 7-pseudo-steroids 1c has been achieved from trenbolone 3 via an efficient 14 step sequence with overall yields of 10-15%. Various substitutions were incorporated at both the aromatic side chain as well as the D ring. The orientation of aromatic side chain at C10 plays a crucial role for Progesterone Receptor (PR) activity. Compound 2a (T47D=1nM) with -NMe(2) para to the aromatic group along with spirofurane groups in the D ring was the optimal substitution. All compounds were also evaluated for Glucocorticoid Receptor (GR) antagonist activities in vivo in a rat and found efficacious in uterine complement C3 assay via the oral route of administrations.

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