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Updated: Jun 30, 2026
07:41
A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
Small, non-peptide C5a receptor antagonists: part 2.
Julian Blagg1, Charles Mowbray, David Pryde
1Department of Discovery Chemistry, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK.
Bioorganic & Medicinal Chemistry Letters
|September 23, 2008
Summary
Highly potent C5a receptor antagonists were synthesized via alpha-amide substitution. Further modifications aimed to enhance compound polarity by adding basic centers or incorporating heterocycles.
Area of Science:
- Medicinal Chemistry
- Pharmacology
Background:
- The C5a receptor (C5aR) plays a crucial role in inflammatory responses.
- Inhibiting C5aR is a therapeutic strategy for various inflammatory diseases.
Purpose of the Study:
- To synthesize novel and potent C5a receptor antagonists.
- To explore methods for improving the physicochemical properties of these antagonists, specifically polarity.
Main Methods:
- Synthesis of C5a receptor antagonists starting from compound 2.
- Utilized alpha-amide substitution for antagonist development.
- Introduced basic centers and incorporated weakly basic heterocycles to modulate polarity.
Main Results:
- Several highly potent C5a receptor antagonists were successfully synthesized.
- The introduction of basic centers and heterocycles demonstrated an effect on compound polarity.
Conclusions:
- Alpha-amide substitution is an effective strategy for generating potent C5a receptor antagonists.
- Strategies for increasing polarity were explored, offering potential for optimized drug candidates.
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