Design and synthesis of benzo-lipoxin A4 analogs with enhanced stability and potent anti-inflammatory properties
Document Type
Article
Publication Title
Bioorganic and Medicinal Chemistry Letters
Abstract
A new class of chemically and metabolically stable lipoxin analogs featuring a replacement of the tetraene unit of native LXA4 with a substituted benzo-fused ring system have been designed and studied. These molecules were readily synthesized via a convergent synthetic route involving iterative palladium-mediated cross-coupling, and exhibit enhanced chemical stability, as well as resistance to metabolic inactivation via eicosanoid oxido-reductase. These new LX analogs were evaluated in a model of acute inflammation and were shown to exhibit potent anti-inflammatory properties, significantly decreasing neutrophil infiltration in vivo. The most potent among these was compound 9 (o-[9,12]-benzo-15-epi-LXA4 methyl ester. Taken together, these findings help identify a new class of stable and easily prepared LX analogs that may serve as novel tools and as promising leads for new anti-inflammatory agents with improved therapeutic profile. © 2008 Elsevier Ltd. All rights reserved.
First Page
1382
Last Page
1387
DOI
10.1016/j.bmcl.2008.01.013
Publication Date
2-15-2008
Recommended Citation
Petasis, Nicos A.; Keledjian, Raquel; Sun, Yee Ping; Nagulapalli, Kalyan C.; Tjonahen, Eric; Yang, Rong; and Serhan, Charles N., "Design and synthesis of benzo-lipoxin A4 analogs with enhanced stability and potent anti-inflammatory properties" (2008). Pharmaceutical and Administrative Sciences Faculty Publications. 126.
https://doi.org/10.1016/j.bmcl.2008.01.013
https://collections.uhsp.edu/pharm-admin-sciences_pubs/126
