Synthesis and Profiling of a Diverse Collection of Azetidine-Based Scaffolds for the Development of CNS-Focused Lead-like Libraries
| Autor: | Carol A. Mulrooney, Morgan Welzel-O’Shea, Bérénice C. Lemercier, Edward B. Holson, Landon Durak, Sarathy Kesavan, Jeremy R. Duvall, Jingqiang Wei, Florence F. Wagner, Adrien Joliton, Laura M. Panko, Maurice D. Lee, Lisa A. Marcaurelle, Lakshmi B. Akella, Haibo Liu, Emeline L. Davoine, Jason T. Lowe, Méryl Thomas, Etienne J. Donckele, Michael Foley, Byung-Chul Suh, Giovanni Muncipinto, Ann Rowley, Jean-Charles Marie, Baudouin Gerard |
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| Rok vydání: | 2012 |
| Předmět: |
Central Nervous System
Cell Membrane Permeability Molecular Structure Extramural Organic Chemistry Azetidine Endothelial Cells Stereoisomerism Combinatorial chemistry Article Small Molecule Libraries Mice chemistry.chemical_compound Solubility chemistry Animals Azetidines Humans Spiro Compounds Caco-2 Cells |
| Zdroj: | The Journal of Organic Chemistry. 77:7187-7211 |
| ISSN: | 1520-6904 0022-3263 |
| DOI: | 10.1021/jo300974j |
| Popis: | The synthesis and diversification of a densely functionalized azetidine ring system to gain access to a wide variety of fused, bridged, and spirocyclic ring systems is described. The in vitro physicochemical and pharmacokinetic properties of representative library members are measured in order to evaluate the use of these scaffolds for the generation of lead-like molecules to be used in targeting the central nervous system. The solid-phase synthesis of a 1976-membered library of spirocyclic azetidines is also described. |
| Databáze: | OpenAIRE |
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