Thiophene-Containing Lipoxin A4 Analogues: Synthesis and Their Effect on the Production of Key Cytokines

  • Colm Duffy
Part of the Springer Theses book series (Springer Theses)


It has recently been demonstrated that replacement of the triene system, present in native LXA4 and LXB4 with benzene, increases the increases the stability of these eicosanoids to enzymatic metabolism [1, 2, 3] In  Chap. 4, we demonstrated that the addition of a heteroatom can also enhance the bioactivity. This pyridine-containing analogue displayed an impressive ability to resolve the inflammation process [4]. In an extension to this work, we sought to replace the triene system with a thiophene ring, Fig. 5.1, and examine the effect this substitution has on the biological potency of the compound. This substitution is a classical example of the bioisoterism concept in medicinal chemistry [5, 6]. Thiophene is an excellent bioisostere for benzene, as the diameter of the sulphur atom is the same length of the replaced C=C double bond [7]. It also offers the possibility of accessing three positional isomers of the analogue which can assist in probing the compounds bioactivity. This particular drug design approach is common and accounts for a large proportion of the successful examples of bioisosteric replacement which can be seen in the literature [8, 9, 10].
Fig. 5.1

Design of thiophene-containing LXA4 analogue 2


Cross Coupling Silyl Ether Vinyl Carbon Pyridinium Chlorochromate Cross Metathesis 
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© Springer-Verlag Berlin Heidelberg  2012

Authors and Affiliations

  1. 1.UCD School of Chemistry and Chemical Biology, Centre for Synthesis and Chemical BiologyUniversity College DublinBelfield, Dublin 4Ireland

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