Short-acting 5-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4(3H)-one derivatives as orally-active calcium-sensing receptor antagonists

Autor:	Scott W. Bagley, Hang T. Nguyen, Kosea S. Frederick, Michael P. Zawistoski, Kenneth J. DiRico, Vishwas M. Paralkar, Xiaojing Yang, Hua Gao, Thanh V. Olson, Keith Riccardi, Stephanie Santucci, F. Christopher Bi, Tristan S. Maurer, Matthew Corbett, Daniel P. Walker, Ryan Michael Kelley, Robert M. Oliver, John William Benbow, David R. Healy, Joseph DiBrinno, Amit S. Kalgutkar, Kevin K.-C. Liu, Mei Li, Syed Ahmed, Mary Theresa Didiuk, Joel Morris, Chiliu Chen, William M. Hungerford, Bruce M. Bechle, Yuan Zeng, Jianke Li, Angel Guzman-Perez, David A. Griffith
Rok vydání:	2009
Předmět:	Male Anabolism Stereochemistry Clinical Biochemistry Administration Oral Pharmaceutical Science chemistry.chemical_element Parathyroid hormone Stimulation Pyrimidinones Calcium Biochemistry Rats Sprague-Dawley Structure-Activity Relationship chemistry.chemical_compound Anabolic Agents Pharmacokinetics Drug Discovery Animals Receptor Molecular Biology Trifluoromethyl Organic Chemistry Rats chemistry Parathyroid Hormone Molecular Medicine Calcium-sensing receptor Receptors Calcium-Sensing
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 19:4555-4559
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2009.07.004
Popis:	Synthesis and structure-activity relationship (SAR) studies on 5-trifluoromethylpyrido[4,3-d]pyrimidin-4(3H)-ones, a novel class of calcium receptor antagonists is described with particular emphasis on optimization of the pharmacokinetic/pharmacodynamic parameters required for a short duration of action compound. Orally-active compounds were identified which displayed the desired animal pharmacology (rapid and transient stimulation of parathyroid hormone) essential for bone anabolic effects.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::72173b66555bd956618fe8850eb6bbd3 https://doi.org/10.1016/j.bmcl.2009.07.004 Zobrazit plný text záznamu Full Text from ScienceDirect