Discovery of 5-phenoxy-1,3-dimethyl-1H-pyrazole-4-carboxamides as potent agonists of TGR5 via sequential combinatorial libraries

Autor:	Joseph S. Warmus, Markus Boehm, David W. Piotrowski, Terri Hinchey, Joanne Buxton, Janice E. Chin, Ann M. Janssen, Kentaro Futatsugi, Allyn T. Londregan, Philip A. Carpino, Nicole S. Roush
Rok vydání:	2013
Předmět:	Agonist Stereochemistry medicine.drug_class Clinical Biochemistry Pharmaceutical Science Pyrazole Biochemistry Receptors G-Protein-Coupled Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Combinatorial Chemistry Techniques Humans Potency Molecular Biology Chemotype Chemistry Organic Chemistry Amides Combinatorial chemistry G protein-coupled bile acid receptor In vitro Peripheral blood Pyrazoles Molecular Medicine Functional activity
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 23:1407-1411
ISSN:	0960-894X
Popis:	Optimization of a high-throughput screening hit led to the discovery of a new series of 5-phenoxy-1,3-dimethyl-1H-pyrazole-4-carboxamides as highly potent agonists of TGR5. This novel chemotype was rapidly developed through iterative combinatorial library synthesis. It was determined that in vitro agonist potency correlated with functional activity data from human peripheral blood monocytes.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cc843cd3afae23d85020b3a102b77e5f https://doi.org/10.1016/j.bmcl.2012.12.076 Zobrazit plný text záznamu Full Text from ScienceDirect