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ChemMedChem
; 12(13): 1045-1054, 2017 07 06.
Article
En
| MEDLINE
| ID: mdl-28544630
Herein we describe the synthesis and biological evaluation of a series of novel benzothiazoles based on a diaryl urea scaffold previously reported in some allosteric chemokine receptorâ 2 (CXCR2) inhibitors. From a library of 41 new compounds, 17 showed significant inhibition of CXCR2, with IC50 values less than 10â µm and selectivity over CXCR4. Our ADMET simulations suggest favorable drug-like properties for the active compounds. Importantly, we developed a predictive model that can distinguish active from inactive compounds; this will serve as a valuable tool to guide the design of optimized compounds to be evaluated in preclinical models.
Benzothiazoles/pharmacology , Phenylurea Compounds/pharmacology , Receptors, Interleukin-8B/antagonists & inhibitors , Benzothiazoles/chemical synthesis , Benzothiazoles/toxicity , Cell Line, Tumor , Humans , Models, Molecular , Phenylurea Compounds/chemical synthesis , Phenylurea Compounds/toxicity , Receptors, CXCR4/antagonists & inhibitors , Structure-Activity Relationship , beta-Arrestin 2/metabolism