Discovery of N-[(2S)-5-(6-fluoro-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide, a novel clinical AMPA receptor positive modulator

Autor:	Kathrine J. Smith, Roberto Profeta, Simon E. Ward, Marta Neve, Simone Spada, Beatrice Oliosi, Jesper Lund, Andrew Jonathan Harris, Anna Mingardi, Claudette Mookherjee, Stuart P. Ballantine, Rosemary A. Melarange, Laura Aldegheri, Andy J. Harker, Benjamin D. Bax, Mark H Harries, Kevin M. Thewlis, Paul W. Smith, Daniele Andreotti, J. Mosley, Shahnaz P. Yusaf
Rok vydání:	2010
Předmět:	Male Models Molecular Pyridines education Allosteric regulation Administration Oral Biological Availability AMPA receptor Pharmacology Crystallography X-Ray Cns penetration Cell Line Rats Sprague-Dawley chemistry.chemical_compound Structure-Activity Relationship Dogs Pharmacokinetics Allosteric Regulation Species Specificity Preclinical pharmacokinetics Drug Discovery Animals Humans Receptors AMPA Sulfonamides Chemistry Callithrix Stereoisomerism Blood Proteins humanities Protein Structure Tertiary Rats Macaca fascicularis Indenes Blood-Brain Barrier Microsomes Liver Molecular Medicine Penetrant (biochemical) Protein Binding
Zdroj:	Journal of medicinal chemistry. 53(15)
ISSN:	1520-4804
Popis:	A series of AMPA receptor positive allosteric modulators has been optimized from poorly penetrant leads to identify molecules with excellent preclinical pharmacokinetics and CNS penetration. These discoveries led to 17i, a potent, efficacious CNS penetrant molecule with an excellent pharmacokinetic profile across preclinical species, which is well tolerated and is also orally bioavailable in humans.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::154b627b7254de36c15c9e847ad6636c https://pubmed.ncbi.nlm.nih.gov/20614889 Zobrazit plný text záznamu