Estrogen receptor ligands. Part 10: Chromanes: old scaffolds for new SERAMs

Autor:	Donald B. Kimmel, Lee Yuh Pai, Carolyn DaSilva, Paula M.D. Fitzgerald, Nandini Sharma, Alfred A. Reszka, Wanda Chan, Milton L. Hammond, Elizabeth T. Birzin, Yi Tien Yang, Lawrence F. Colwell, Susan Li, Hilary A. Wilkinson, Sharon Adamski, Qiang Tan, Jerry D. Morgan, Leonard P. Freedman, Edward C. Hayes, James M. Schaeffer, John E. Fisher, Susan P. Rohrer, Timothy A. Blizzard, Frank P. DiNinno, Sudha Warrier, Joel B. Yudkovitz
Rok vydání:	2005
Předmět:	Selective Estrogen Receptor Modulators medicine.medical_specialty Clinical Biochemistry Gene Expression Pharmaceutical Science Estrogen receptor Ligands Biochemistry Bone resorption Cell Line Rats Sprague-Dawley Structure-Activity Relationship In vivo Internal medicine Drug Discovery medicine Animals Humans Chromans Molecular Biology Binding Sites Molecular Structure Chemistry Cell growth Uterus Organic Chemistry Estrogen Receptor alpha Organ Size Antiestrogen Rats Resorption Endocrinology Models Chemical Molecular Medicine Female Signal transduction Estrogen receptor alpha Protein Binding
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 15:1675-1681
ISSN:	0960-894X
Popis:	The discovery, synthesis, and SAR of chromanes as ERα subtype selective ligands are described. X-ray studies revealed that the origin of the ERα-selectivity resulted from a C-4 trans methyl substitution to the cis-2,3-diphenyl-chromane platform. Selected compounds from this class demonstrated very potent in vivo antagonism of estradiol in an immature rat uterine weight assay, effectively inhibited ovariectomy-induced bone resorption in a 42 days treatment paradigm, and lowered serum cholesterol levels in ovx’d adult rat models. The best antagonists 8F and 12F also exhibited potent inhibition of MCF-7 cell growth and were shown to be estrogen receptor down-regulators (SERDs).
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ae0224c0d631c57c9693d89abf0b9455 https://doi.org/10.1016/j.bmcl.2005.01.046 Zobrazit plný text záznamu Full Text from ScienceDirect