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Updated: May 29, 2026
09:04
A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products
Published on: September 9, 2016
Acidic triazoles as soluble guanylate cyclase stimulators
Lee R Roberts1, Paul A Bradley, Mark E Bunnage
1Worldwide Medicinal Chemistry, Pfizer, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. lee.roberts@pfizer.com
Bioorganic & Medicinal Chemistry Letters
|September 20, 2011
Summary
Researchers developed novel acidic triazoles that stimulate soluble guanylate cyclase. Adding a trifluoromethyl (CF3) group enhanced the drug-like properties, as shown by compound 25.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Organic Synthesis
Background:
- Soluble guanylate cyclase (sGC) is a key enzyme in cardiovascular regulation.
- sGC stimulators offer therapeutic potential for various diseases.
- Optimizing physicochemical properties is crucial for drug development.
Purpose of the Study:
- To synthesize and characterize novel acidic triazoles as potential sGC stimulators.
- To investigate the impact of trifluoromethyl (CF3) group incorporation on molecular properties.
- To identify lead compounds with improved drug-like characteristics.
Main Methods:
- Synthesis of a series of acidic triazole derivatives.
- Evaluation of soluble guanylate cyclase (sGC) stimulatory activity.
- Assessment of physicochemical properties, including lipophilicity and solubility.
- Structure-activity relationship (SAR) analysis.
Main Results:
- Several acidic triazoles demonstrated significant sGC stimulatory activity.
- Incorporation of the trifluoromethyl (CF3) moiety enhanced lipophilicity and metabolic stability.
- Compound 25 exhibited a favorable profile of activity and drug-like properties.
Conclusions:
- Acidic triazoles represent a promising class of sGC stimulators.
- The CF3 group is a valuable substituent for optimizing the properties of sGC modulators.
- Compound 25 serves as a lead candidate for further preclinical development.
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