874827-19-7Relevant academic research and scientific papers
Development and characterization of new inhibitors of the human and mouse hematopoietic prostaglandin D2 synthases
Christ, Angelika N.,Labzin, Larisa,Bourne, Gregory T.,Fukunishi, Hirotada,Weber, Jane E.,Sweet, Matthew J.,Smythe, Mark L.,Flanagan, Jack U.
experimental part, p. 5536 - 5548 (2010/11/17)
The hematopoietic prostaglandin D2 synthase has a proinflammatory effect in a range of diseases, including allergic asthma, where its product prostaglandin D2 (PGD2) has a role in regulating many of the hallmark disease characteristics. Here we describe the development and characterization of a novel series of hematopoietic prostaglandin D2 synthase inhibitors with potency similar to that of known inhibitors. Compounds N-benzhydryl-5-(3-hydroxyphenyl)thiophene-2- carboxamide (compound 8) and N-(1-amino-1-oxo-3-phenylpropan-2-yl)-6-(thiophen- 2-yl)nicotinamide (compound 34) demonstrated low micromolar potency in the inhibition of the purified enzyme, while only 34 reduced Toll-like receptor (TLR) inducible PGD2 production in both mouse primary bone marrow-derived macrophages and the human megakaryocytic cell line MEG-01S. Importantly, 34 demonstrated a greater selectivity for inhibition of PGD 2 synthesis versus other eicosanoids that lie downstream of PGH 2 (PGE2 and markers of prostacyclin (6-keto PGF 1?) and thromboxane (TXB2)) when compared to the known inhibitors HQL-79 (compound 1) and 2-phenyl-5-(1H-pyrazol-3-yl)thiazole (compound 2). Compound 34 therefore represents a selective hematopoietic prostaglandin D2 synthase inhibitor.
