Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ER alpha plus Breast Cancer

作者：Burks Heather E^*; Abrams Tinya; Kirby Christina A; Baird Jason; Fekete Alexander; Hamann Lawrence G; Kim Sunkyu; Lombardo Franco; Loo Alice; Lubicka Danuta; Macchi Kaitlin; McDonnell Donald P; Mishina Yuji; Norris John D; Nunez Jill; Saran Chitra; Sun Yingchuan; Thomsen Noel M; Wang Chunrong; Wang Jianling; Peukert Stefan

来源：Journal of Medicinal Chemistry, 2017, 60(7): 2790-2818.

DOI：10.1021/acs.jmedchem.6b01468

Tetrahydroisoquinoline 40 has been identified as a potent ER alpha antagonist and selective estrogen receptor degrader (SERD), exhibiting good oral bioavailability, antitumor efficacy, and SERD activity in vivo. We outline the discovery and chemical optimization of the THIQ scaffold leading to THIQ 40 and showcase the racemization of the scaffold, pharmacokinetic studies in preclinical species, and the in vivo efficacy of THIQ 40 in a MCF-7 human breast cancer xenograft model.

• 出版日期2017-4-13