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Agonist/antagonist modulation in a series of 2-aryl benzimidazole H4 receptor ligands.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 Jun 01; Vol. 20 (11), pp. 3367-71. Date of Electronic Publication: 2010 Apr 11. - Publication Year :
- 2010
-
Abstract
- The present work details the transformation of a series of human histamine H(4) agonists into potent functional antagonists. Replacement of the aminopyrrolidine diamine functionality with a 5,6-fused pyrrolopiperidine ring system led to an antagonist. The dissection of this fused diamine led to the eventual replacement with heterocycles. The incorporation of histamine as the terminal amine led to a very potent and selective histamine H(4) agonist; whereas incorporation of the constrained histamine analog, spinacamine, modulated the functional activity to give a partial agonist. In two separate series, we demonstrate that constraining the terminal amino portion modulated the spectrum of functional activity of histamine H(4) ligands.<br /> (Copyright 2010 Elsevier Ltd. All rights reserved.)
- Subjects :
- Benzimidazoles chemistry
Histamine Agonists chemistry
Histamine Antagonists chemistry
Humans
Ligands
Receptors, G-Protein-Coupled metabolism
Receptors, Histamine metabolism
Receptors, Histamine H4
Structure-Activity Relationship
Benzimidazoles pharmacology
Histamine Agonists pharmacology
Histamine Antagonists pharmacology
Receptors, G-Protein-Coupled drug effects
Receptors, Histamine drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 20
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 20452213
- Full Text :
- https://doi.org/10.1016/j.bmcl.2010.04.017