Jain Nareshkumar, Allan George, Linton Olivia, Tannenbaum Pamela, Chen Xin, Xu Jun, Zhu Peifang, Gunnet Joseph, Demarest Keith, Lundeen Scott, Murray William, Sui Zhihua
Johnson and Johnson Pharmaceutical Research and Development, Medicinal Chemistry, LLC, Exton, PA 19341, USA.
Bioorg Med Chem Lett. 2009 Jul 15;19(14):3977-80. doi: 10.1016/j.bmcl.2009.01.095. Epub 2009 Jan 31.
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.
通过14步高效反应序列，已从群勃龙3合成出新型7-假甾体1c，总产率为10 - 15%。在芳族侧链以及D环上引入了各种取代基。C10位芳族侧链的取向对孕酮受体（PR）活性起着关键作用。在芳族基团对位带有-NMe(2)以及在D环带有螺呋喃基团的化合物2a（T47D = 1nM）是最佳取代物。所有化合物还在大鼠体内评估了糖皮质激素受体（GR）拮抗剂活性，并且发现在子宫补体C3测定中通过口服给药途径有效。
