Synthesis and antitumor activities of 3-modified 2-methoxyestradiol analogs
作者:Lita S. Suwandi、Gregory E. Agoston、Jamshed H. Shah、Arthur D. Hanson、Xiaoguo H. Zhan、Theresa M. LaVallee、Anthony M. Treston
DOI:10.1016/j.bmcl.2009.09.009
日期:2009.11
The syntheses of 2-methoxyestradiol analogs with modifications at the 3-position are described. The analogs were assessed for their antiproliferative, antiangiogenic, and estrogenic activities. Several lead substituents were identified with similar or improved antitumor activities and reduced metabolic liability compared to 2-methoxyestradiol. (C) 2009 Elsevier Ltd. All rights reserved.
Synthesis, antiproliferative, and pharmacokinetic properties of 3- and 17-double-modified analogs of 2-methoxyestradiol
作者:Gregory E. Agoston、Jamshed H. Shah、Lita Suwandi、Arthur D. Hanson、Xiaoguo Zhan、Theresa M. LaVallee、Victor Pribluda、Anthony M. Treston
DOI:10.1016/j.bmcl.2009.08.020
日期:2009.11
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 anti-proliferative 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. (C) 2009 Elsevier Ltd. All rights reserved.