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  • Synthesis, antiproliferative, and pharmacokinetic properties of 3- and 17-double-modified analogs of 2-methoxyestradiol.

Synthesis, antiproliferative, and pharmacokinetic properties of 3- and 17-double-modified analogs of 2-methoxyestradiol.

Bioorganic & medicinal chemistry letters (2009-09-29)
Gregory E Agoston, Jamshed H Shah, Lita Suwandi, Arthur D Hanson, Xiaoguo Zhan, Theresa M LaVallee, Victor Pribluda, Anthony M Treston
PMID19782564
ABSTRACT

The syntheses of 21 analogs of 2-methoxyestradiol are presented, including ENMD-1198 which was selected for advancement into Phase 1 clinical trials in oncology. These analogs were evaluated for antiproliferative activity using breast tumor MDA-MB-231 cells, for antiangiogenic activity in HUVEC proliferation assays, and for estrogenic activity in MCF-7 cell proliferation. The most active analogs were evaluated for iv and oral pharmacokinetic properties via cassette dosing in rat and in mice pharmacokinetic models.