Estrogen receptor ligands. Part 16: 2-Aryl indoles as highly subtype selective ligands for ERα

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Abstract

A novel class of indole ligands for estrogen receptor α have been discovered which exhibit potent affinity and high selectivity. Substitution of the bazedoxifene skeleton to the linker present in the HTS lead 1a provided 22b which was found to be 130-fold α-selective and acted as an antagonist of estradiol activity in uterine tissue and MCF-7 cancer cells.

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A novel class of indole ligands for estrogen receptor α have been discovered which exhibit potent affinity and high selectivity. Substitution of the bazedoxifene skeleton to the linker present in the HTS lead 1a provided 22b which was found to be 130-fold α-selective and acted as an antagonist of estradiol activity in uterine tissue and MCF-7 cancer cells.

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Acknowledgments

The senior author greatfully acknowledges the guidance and mentorship of Dr. Frank DiNinno, whose dedication to this and other efforts over his illustrious career at Merck will always be fondly remembered. The authors thank Dr. Mats Carlquist and his colleagues at Karo-Bio for providing protein samples and diffraction data. Use of the Advanced Photon Source beamline 17-ID was supported by the companies of the Industrial Macromolecular Crystallography Association through a contract with Illinois

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