1196993-69-7Relevant academic research and scientific papers
Discovery of a series of potent and selective human H4 antagonists using ligand efficiency and libraries to explore structure-activity relationship (SAR)
Masood, M.Abid,Selby, Matthew D.,Bell, Andrew S.,Mansfield, Andrew C.,Gardner, Mark,Smith, Graham F.,Smith, Charlotte Lane,Kenyon-Edwards, Helen,Osborne, Rachel,Jones, Rhys M.,Liu, Wai L.,Brown, Christopher D.,Clarke, Nicholas,Perrucio, Francesca,Mowbray, Charles E.
body text, p. 6591 - 6595 (2011/12/04)
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.
2,4-Diaminopyrimidines as histamine H4 receptor ligands-Scaffold optimization and pharmacological characterization
Sander, Kerstin,Kottke, Tim,Tanrikulu, Yusuf,Proschak, Ewgenij,Weizel, Lilia,Schneider, Erich H.,Seifert, Roland,Schneider, Gisbert,Stark, Holger
experimental part, p. 7186 - 7196 (2010/03/03)
The human histamine H4 receptor (hH4R) is a promising new target in the therapy of inflammatory diseases and disorders of the immune system. For the development of new H4R antagonists a broad ligand-based virtual screening was performed resulting in two hits. The dissection of their common annelated aromatic core into its heteromonocyclic components showed that 2,4-diaminopyrimidine is a potent hH4R affinity scaffold, which was comprehensively investigated. Structure-activity relationship studies revealed that slight structural changes evoke extensive differences in functional activities and potencies: while o- and p-substituted benzyl amines mainly showed partial agonism, m-substituted and rigidified ones exhibited inverse agonist efficacy.
