Discovery of novel dihydrobenzofuran cyclopropane carboxylic acid based calcium sensing receptor antagonists for the treatment of osteoporosis

Autor:	Changyou Zhou, David Sutton, Hong Li, Shaoqiang Huang, Xianghong Huo, Hilary A. Wilkinson, Haisheng Wang, Lusong Luo, Dennis M. Zaller, Hank Wang, Gui-Bai Liang, Wei Tang, Peter T. Meinke, Xuelin Yang
Rok vydání:	2016
Předmět:	Cyclopropanes 0301 basic medicine Carboxylic acid Clinical Biochemistry Drug Evaluation Preclinical Administration Oral Pharmaceutical Science Parathyroid hormone 030209 endocrinology & metabolism Biochemistry Anabolic Agents Cyclopropane Rats Sprague-Dawley Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Discovery Animals Structure–activity relationship Receptor Molecular Biology Benzofurans chemistry.chemical_classification Organic Chemistry Small molecule Rats 030104 developmental biology chemistry Parathyroid Hormone Osteoporosis Molecular Medicine Female Calcium-sensing receptor Receptors Calcium-Sensing Half-Life Protein Binding
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 26:4077-4080
ISSN:	0960-894X
Popis:	In a search for novel small molecule calcium-sensing receptor (CaSR) antagonists as oral bone anabolic agents, we discovered dihydrobenzofuran cyclopropane carboxylic acid derivatives, such as 12f (IC50=27.6nM), are highly potent calcium-sensing receptor antagonists. Studies in rats established that compound 12f stimulates parathyroid hormone (PTH) release in a fast-acting, pulsatile manner.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f078ae5162ed552aafd261a817ec8cda https://doi.org/10.1016/j.bmcl.2016.06.073 Zobrazit plný text záznamu Full Text from ScienceDirect