title: Formyl peptide receptor modulators: a patent review and potential applications for inflammatory diseases (2012-2015).
abstract: 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.
authors.affiliation: a Graduate Institute of Natural Products, School of Traditional Medicine, College of Medicine , Chang Gung University , Taoyuan , Taiwan.|b Graduate Institute of Clinical Medical Sciences, College of Medicine , Chang Gung University , Taoyuan , Taiwan.|c Department of Anesthesiology , Chang Gung Memorial Hospital , Taoyuan , Taiwan.
authors.forename: Yung-Fong
authors.initials: YF
authors.lastname: Tsai
authors.affiliation: d Department of Anesthesiology , Taipei Veterans General Hospital and National Yang-Ming University , Taipei , Taiwan.|e Division of Natural Products, Graduate Institute of Biomedical Sciences, College of Medicine , Chang Gung University , Taoyuan , Taiwan.
authors.forename: Shun-Chin
authors.initials: SC
authors.lastname: Yang
authors.affiliation: a Graduate Institute of Natural Products, School of Traditional Medicine, College of Medicine , Chang Gung University , Taoyuan , Taiwan.|c Department of Anesthesiology , Chang Gung Memorial Hospital , Taoyuan , Taiwan.|e Division of Natural Products, Graduate Institute of Biomedical Sciences, College of Medicine , Chang Gung University , Taoyuan , Taiwan.|f Chinese Herbal Medicine Research Team, Healthy Aging Research Centre , Chang Gung University , Taoyuan , Taiwan.|g Research Center for Industry of Human Ecology and Graduate Institute of Health Industry Technology , Chang Gung University of Science and Technology , Taoyuan , Taiwan.
authors.forename: Tsong-Long
authors.initials: TL
authors.lastname: Hwang
keywords: Formyl peptide receptor; inflammatory diseases; leukocyte; pattern recognition receptor