Discovery and optimization of substituted 1-(1-phenyl-1H-pyrazol-3-yl)methanamines as potent and efficacious type II calcimimetics

Autor:	Yuhua Yang, Steve F. Poon, Jeff D. Reagan, David J. St. Jean, Fred D. Lott, Charles Henley, Jenny Ying-Lin Lu, James Davis, Paul E. Harrington, Christopher H. Fotsch, Sean Morony
Rok vydání:	2009
Předmět:	Male Calcimimetic Stereochemistry Administration Oral Biological Availability Stereoisomerism Pyrazole Crystallography X-Ray Chemical synthesis Cell Line Rats Sprague-Dawley chemistry.chemical_compound Methylamines Structure-Activity Relationship In vivo Drug Discovery Phenethylamines medicine Structure–activity relationship Animals Humans Aniline Compounds Molecular Structure Propylamines Chemistry Biological activity medicine.disease Rats Parathyroid Hormone Molecular Medicine Pyrazoles Secondary hyperparathyroidism Hyperparathyroidism Secondary Receptors Calcium-Sensing
Zdroj:	Journal of medicinal chemistry. 52(21)
ISSN:	1520-4804
Popis:	Our efforts to discover potent, orally bioavailable type II calcimimetic agents for the treatment of secondary hyperparathyroidism focused on the development of ring constrained analogues of the known calcimimetic R-568. The structure-activity relationships of various substituted heterocycles and their effects on the human calcium-sensing receptor are discussed. Pyrazole 15 was shown to be efficacious in a rat in vivo pharmacodynamic model.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bc9f6898ca381a10c9ccf357ab442ca9 https://pubmed.ncbi.nlm.nih.gov/19835382 Zobrazit plný text záznamu