Discovery of a series of potent and selective human H4 antagonists using ligand efficiency and libraries to explore structure-activity relationship (SAR)
| Autor: | Francesca Perrucio, M. Abid Masood, Graham Smith, Charles E. Mowbray, M. J. Gardner, Helen Kenyon-Edwards, Charlotte Alice Louise Lane, Rhys M. Jones, Andrew Simon Bell, Wai L. Liu, Andrew C. Mansfield, Matthew D. Selby, Nick Clarke, Christopher D. Brown, Rachel Osborne |
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| Rok vydání: | 2011 |
| Předmět: |
Ligand efficiency
Chemistry Organic Chemistry Clinical Biochemistry Histamine Antagonists Pharmaceutical Science Stereoisomerism Hit to lead Ligands Biochemistry Combinatorial chemistry Receptors G-Protein-Coupled Small Molecule Libraries Structure-Activity Relationship Drug Discovery Molecular Medicine Structure–activity relationship Humans Receptors Histamine Histamine H4 receptor Antagonism Molecular Biology Receptors Histamine H4 |
| Zdroj: | Bioorganicmedicinal chemistry letters. 21(21) |
| ISSN: | 1464-3405 |
| Popis: | We describe the identification of a potent, selective lead series that shows antagonism against the human histamine H4 receptor from thirteen actives identified in an HTS as part of a hit to lead program. By focusing on ligand efficiency and concurrently using a diversity based approach, compounds based around 2,4-diaminopyrimidine were identified with compound 25 being quickly shown to be a good lead. It also had the highest ligand efficiency in the series. |
| Databáze: | OpenAIRE |
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