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Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions
Published on: July 17, 2020
2-(1H-Pyrazol-4-yl)acetic acids as CRTh2 antagonists
Miriam Andrés1, Mónica Bravo, Maria Antonia Buil
1Almirall R&D Centre, Laureano Miró, 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain.
Bioorganic & Medicinal Chemistry Letters
|April 23, 2013
Summary
Researchers discovered pyrazole-4-acetic acid compounds that act as chemoattractant receptor expressed on T helper 2 cells (CRTh2) antagonists. Further optimization yielded potent low nanomolar inhibitors with a well-defined structure-activity relationship (SAR).
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Drug Discovery
Background:
- The chemoattractant receptor expressed on T helper 2 cells (CRTh2) is a key target in inflammatory diseases.
- Identifying novel antagonists for CRTh2 is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To identify and optimize novel CRTh2 receptor antagonists.
- To explore the structure-activity relationship (SAR) of identified antagonists.
Main Methods:
- High throughput screening (HTS) was employed to identify initial hit compounds.
- Iterative chemical synthesis and biological evaluation were used for lead optimization.
Main Results:
- The pyrazole-4-acetic acid substructure emerged as a promising scaffold for CRTh2 antagonism.
- Optimization efforts led to compounds with a tight structure-activity relationship.
- Several low nanomolar CRTh2 inhibitors were successfully identified.
Conclusions:
- Pyrazole-4-acetic acid derivatives represent a viable class of CRTh2 receptor antagonists.
- The identified inhibitors demonstrate significant potential for further development in treating CRTh2-mediated conditions.
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