1622308-76-2Relevant academic research and scientific papers
Discovery of LSZ102, a potent, orally bioavailable selective estrogen receptor degrader (SERD) for the treatment of estrogen receptor positive breast cancer
Tria, George S.,Abrams, Tinya,Baird, Jason,Burks, Heather E.,Firestone, Brant,Gaither, L. Alex,Hamann, Lawrence G.,He, Guo,Kirby, Christina A.,Kim, Sunkyu,Lombardo, Franco,Macchi, Kaitlin J.,McDonnell, Donald P.,Mishina, Yuji,Norris, John D.,Nunez, Jill,Springer, Clayton,Sun, Yingchuan,Thomsen, Noel M.,Wang, Chunrong,Wang, Jianling,Yu, Bing,Tiong-Yip, Choi-Lai,Peukert, Stefan
, p. 2837 - 2864 (2018/04/23)
In breast cancer, estrogen receptor alpha (ERα) positive cancer accounts for approximately 74% of all diagnoses, and in these settings, it is a primary driver of cell proliferation. Treatment of ERα positive breast cancer has long relied on endocrine therapies such as selective estrogen receptor modulators, aromatase inhibitors, and selective estrogen receptor degraders (SERDs). The steroid-based anti-estrogen fulvestrant (5), the only approved SERD, is effective in patients who have not previously been treated with endocrine therapy as well as in patients who have progressed after receiving other endocrine therapies. Its efficacy, however, may be limited due to its poor physicochemical properties. We describe the design and synthesis of a series of potent benzothiophene-containing compounds that exhibit oral bioavailability and preclinical activity as SERDs. This article culminates in the identification of LSZ102 (10), a compound in clinical development for the treatment of ERα positive breast cancer.
COMPOUNDS AND COMPOSITIONS AS SELECTIVE ESTROGEN RECEPTOR DEGRADERS
-
Paragraph 0286; 0287, (2014/09/03)
The present invention relates to compounds of formula I: in which n, m, X, Y1, R1, R2, R3, R4 and R5 are defined in the Summary of the Invention; capable of being both potent antagonists and degraders of estrogen receptors. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds and compositions in the management of diseases or disorders associated with aberrant estrogen receptor activity.
