1,2,4-Triazolyl 5-Azaspiro[2.4]heptanes: Lead Identification and Early Lead Optimization of a New Series of Potent and Selective Dopamine D3 Receptor Antagonists

Autor:	Aldo Feriani, Laura Zonzini, Laura Castelletti, Selena Nola, Michele Dal Cin, Teresa Semeraro, Sylvie Gehanne, Silvia Tomelleri, Filippo Visentini, Palmina Cavallini, Susanna Cremonesi, Annalisa Pellacani, Anna Sava, Alessia Bacchi, Andrea Wong, Simone Braggio, Luca Tarsi, Mahmud Kajbaf, Paolo Cavanni, Elisabetta Perdona, Christian Heidbreder, Luciano Marchiò, Beatrice Oliosi, Fabrizio Micheli
Rok vydání:	2016
Předmět:	Models Molecular 0301 basic medicine Stereochemistry hERG CHO Cells Crystallography X-Ray 030226 pharmacology & pharmacy Heptanes Structure-Activity Relationship 03 medical and health sciences Cricetulus 0302 clinical medicine In vivo Dopamine receptor D3 Dopamine Drug Discovery medicine Animals Humans Structure–activity relationship Spiro Compounds biology Chemistry Receptors Dopamine D3 Triazoles biology.organism_classification Ether-A-Go-Go Potassium Channels In vitro 030104 developmental biology biology.protein Molecular Medicine Selectivity medicine.drug
Zdroj:	Journal of Medicinal Chemistry. 59:8549-8576
ISSN:	1520-4804 0022-2623
DOI:	10.1021/acs.jmedchem.6b00972
Popis:	A novel series of 1,2,4-triazolyl 5-azaspiro[2.4]heptanes with high affinity and selectivity at the dopamine (DA) D3 receptor (D3R) is described. Some of these compounds also have high selectivity over the hERG channel and were characterized with respect to their pharmacokinetic properties both in vitro and in vivo during lead identification and early lead optimization phases. A few derivatives with overall favorable developability characteristics were selected for further late lead optimization studies.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3e92639ff81d14ff2d424ab7f16b988a https://doi.org/10.1021/acs.jmedchem.6b00972 Zobrazit plný text záznamu