Exploration of Pyrido[3,4-d]pyrimidines as Antagonists of the Human Chemokine Receptor CXCR2

Autor: Max Van Hoof, Sandra Claes, Katrijn Boon, Tom Van Loy, Dominique Schols, Wim Dehaen, Steven De Jonghe
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Molecules, Vol 28, Iss 5, p 2099 (2023)
Druh dokumentu: article
ISSN: 28052099
1420-3049
DOI: 10.3390/molecules28052099
Popis: Upregulated CXCR2 signalling is found in numerous inflammatory, autoimmune and neurodegenerative diseases, as well as in cancer. Consequently, CXCR2 antagonism is a promising therapeutic strategy for treatment of these disorders. We previously identified, via scaffold hopping, a pyrido[3,4-d]pyrimidine analogue as a promising CXCR2 antagonist with an IC50 value of 0.11 µM in a kinetic fluorescence-based calcium mobilization assay. This study aims at exploring the structure–activity relationship (SAR) and improving the CXCR2 antagonistic potency of this pyrido[3,4-d]pyrimidine via systematic structural modifications of the substitution pattern. Almost all new analogues completely lacked the CXCR2 antagonism, the exception being a 6-furanyl-pyrido[3,4-d]pyrimidine analogue (compound 17b) that is endowed with similar antagonistic potency as the original hit.
Databáze: Directory of Open Access Journals
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