The hematopoietic prostaglandin D(2) synthase has a proinflammatory effect in a range of diseases, including allergic asthma, where its product prostaglandin D(2) (PGD(2)) 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 D(2) 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 PGD(2) 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) (PGE(2) and markers of prostacyclin (6-keto PGF(1alpha)) and thromboxane (TXB(2))) 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 D(2) synthase inhibitor.

The reaction of 2-cyclohexen-1-one derivatives with iodine–cerium(IV) ammonium nitrate in alcohols (methanol, ethanol, 1-propanol, 2-propanol, and 1-butanol) under refluxing, gave the corresponding alkyl phenyl ethers in good yields. In the case of diol (ethylene glycol, 1,3-propanediol, and 1,4-butanediol), phenoxyalkanol derivatives were obtained. The present method was also applicable to oxidative rearrangement of isophorone.

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A New Alkoxyiodination and Nitratoiodination of α,β-Unsaturated Ketones and Esters Using Iodine-Cerium(IV) Ammonium Nitrate.-β-Alkoxy-α-bromoketone and ester derivatives are important synthetic intermediates but no study on the β-alkoxy-, β-nitrato-, and β-hydroxy-αiodination of α,β-unsaturated ketones and esters is described in the literature. Thus, the reaction of a,β-unsaturated ketones and esters such as (I) and (VI), resp., with the title reagents in alcohols and acetonitrile is examined.- (HORIUCHI, C. A.; OCHIAI, K.; FUKUNISHI, H.; Chem. Lett. (1994) 2, 185-188; Dep. Chem., Rikkyo St. Paul's Univ., Toshima, Tokyo 171, Japan; EN)