Synthesis, Structure–Activity Relationship Studies, and ADMET Properties of 3‐Aminocyclohex‐2‐en‐1‐ones as Chemokine Receptor 2 (CXCR2) Antagonists
Abstract
Herein we describe the synthesis and structure–activity relationships of 3‐aminocyclohex‐2‐en‐1‐one derivatives as novel chemokine receptor 2 (CXCR2) antagonists. Thirteen out of 44 derivatives were found to inhibit CXCR2 downstream signaling in a Tango assay specific for CXCR2, with IC50 values less than 10 μm. In silico ADMET prediction suggests that all active compounds possess drug‐like properties. None of these compounds show significant cytotoxicity, suggesting their potential application in inflammatory mediated diseases. A structure–activity relationship (SAR) map has been generated to gain better understanding of their binding mechanism to guide further optimization of these new CXCR2 antagonists.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 30, 2018
- Source ID
- 10.1002/cmdc.201800027
Entities
People
- Bikash Debnath
- Nouri Neamati
- Weiyang Dai
- Wenmin Chen
- Yong Wu
Organizations
- China Scholarship Council
- Sichuan University
- United States Department of Defense
- University of Michigan