Synthesis and structure–activity relationships of heteroaryl substituted-3,4-diamino-3-cyclobut-3-ene-1,2-dione CXCR2/CXCR1 receptor antagonists
Graphical abstract
The preparation and biological evaluation of a series of heteroaryl substituted-3,4-diamino-3-cyclobut-3-ene-1,2-dione CXCR2/CXCR1 receptor antagonists (such as 49) is reported.
References and notes (21)
- et al.
J. Biol. Chem.
(1993) Expert Opin. Ther. Patents
(2001)et al.Chem. Rev.
(2003)Curr. Top. Med. Chem.
(2006)- et al.
Synthesis
(1998) - Full experimental details have appeared elsewhere: Taveras, A. G.; Aki, C. J.; Bond, R. W.; Chao, J.; Dwyer, M.;...
- et al.
J. Org. Chem.
(1983) - et al.
J. Org. Chem.
(1993) - et al.
Drug Discov. Today
(1999) - et al.
J. Pharm. Exp. Ther.
(2007) - et al.
Bioorg. Med. Chem. Lett.
(2007)
Cited by (18)
Covalently Immobilized Lipases are Efficient Stereoselective Catalysts for the Kinetic Resolution of rac-(5-Phenylfuran-2-yl)-β-alanine Ethyl Ester Hydrochlorides
2017, European Journal of Organic ChemistryAt-line coupling of LC-MS to bioaffinity and selectivity assessment for metabolic profiling of ligands towards chemokine receptors CXCR1 and CXCR2
2015, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life SciencesCitation Excerpt :Since the exact position of biotransformation is not determined for metabolites M1 and M2, it is difficult to tell if and how the introduction of hydroxyl group influences the bioactivity. However, it can be noted that the SAR studies on MK-7123 analogs showed that the 4,5-disubstituted furan derivatives kept the high affinity for the CXCR2 receptor, while the introduction of the second substituent in other positions in the furan ring led to a drop in affinity [36]. The same study showed that the change of the methyl substituent in the furan ring with a longer branch led to high affinity binders, but there is no information on the affinity of the hydroxymethyl analog of MK-7123.
Diaminocyclobutenediones as potent and orally bioavailable CXCR2 receptor antagonists: SAR in the phenolic amide region
2009, Bioorganic and Medicinal Chemistry LettersFluoroalkyl α side chain containing 3,4-diamino-cyclobutenediones as potent and orally bioavailable CXCR2-CXCR1 dual antagonists
2009, Bioorganic and Medicinal Chemistry Letters3,4-Diamino-1,2,5-thiadiazole as potent and selective CXCR2 antagonists
2009, Bioorganic and Medicinal Chemistry Letters
- †
Present address: Abbott Bioresearch Center, 100 Research Drive, Worcester, MA 01605, USA.
- ‡
Present address: Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USA.