Formyl peptide receptor modulators: a patent review and potential applications for inflammatory diseases (2012-2015)

ABSTRACT

Introduction: The activation of leukocytes and the subsequent immune cascade play an essential role in sterile and infectious inflammation. Dysregulation of these immune responses or excess leukocyte activation can induce tissue damage, organ dysfunction and mortality. Formyl peptide receptors (FPRs) are functionally diverse pattern recognition receptors responsible for recognizing different endogenous damage-associated molecular patterns or exogenous pathogen-associated molecular patterns. FPRs mediate leukocyte activation during inflammation. FPR1 antagonists and FPR2 agonists have demonstrated significant anti-inflammatory effects based on in vitro and in vivo studies. An increasing number of synthesized compounds targeting FPRs, especially potential FPR1 antagonists and FPR2 agonists, have been disclosed in patents.

Areas covered: This article summarizes the current pharmacology patents related to FPR family modulators and their therapeutic indications based on a review of patent applications disclosed between 2012 and 2015.

Expert opinion: In this review, FPR1 modulators comprise β-1,3-glucan synthase inhibitors containing an FPR ligand moiety, template-fixed peptidomimetics, cyclosporin H, and dipeptide derivatives. FPR2 modulators include phenylurea, bridged spiro[2.4]heptane ester, naphthalene, aminotriazole, polycyclic pyrrolidine-2,5-dione, imidazolidine-2,4-dione, (2-ureidoacetamido)alkyl, amide, oxazolyl-methylether, oxazole, thiazole, and crystalline potassium salt derivatives. These compounds have potential applications for human conditions such as inflammatory lung diseases, ischemia-reperfusion injury, sepsis, inflammatory bowel disease, and wound healing. FPRs are emerging as important targets for treating leukocyte-dominant inflammation.

KEYWORDS:

• Formyl peptide receptor
• inflammatory diseases
• leukocyte
• pattern recognition receptor

Article highlights

• In this article, we review all 29 FPR modulator patents that were published from 2012 to 2015. In total, 34 derivatives whose compound formulas were structurally illustrated were suggested as treatments for FPR-related inflammatory diseases.

• All of the disclosed compounds have been divided into two major categories: FPR1 and FPR2 modulators.

• FPR1 modulators include β-1,3-glucan synthase inhibitors containing an FPR ligand moiety, template-fixed peptidomimetics, cyclosporin H, and dipeptide derivatives.

• FPR2 modulators include compounds derived from phenylurea, bridged spiro[2.4]heptane ester, naphthalene, aminotriazole, polycyclic pyrrolidine-2,5-dione, imidazolidine-2,4-dione, (2-ureidoacetamido)alkyl, amide, oxazolyl-methylether, oxazole, thiazole, and crystalline potassium salt.

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Acknowledgments

We would like to acknowledge the assistance of Taylor & Francis Editing Services in editing the final manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded