Pyrazol-3-propanoic acid derivatives as novel inhibitors of leukotriene biosynthesis in human neutrophils.

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Caliskan B, Luderer S, Ozkan Y, Werz O, Banoglu E

Pyrazol-3-propanoic acid derivatives as novel inhibitors of leukotriene biosynthesis in human neutrophils.

Eur J Med Chem. 2011 Oct;46(10):5021-33. doi: 10.1016/j.ejmech.2011.08.009. Epub 2011 Aug 11.

PubMed ID

21868137 [ View in PubMed

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Abstract

We recently presented that compounds 4a-b moderately inhibited leukotriene (LT) formation in human neutrophils. For structural derivatization of 4a-b, novel thirty-six title compounds were synthesized and led to more potent inhibition of LT biosynthesis in activated human neutrophils exemplified by compounds 15, 27-30, 32-37, 41, 42 with IC(50) values in the range of 1.6-3.5 muM. Moreover, compounds 32, 35, 42, 43 and 44 showed a substantial inhibition of platelet COX-1 activity with IC(50) of 2.5, 0.041, 0.3, 0.9 and 0.014 muM, respectively, leading up to dual acting inhibitors. On the basis of their high potency in cellular environment, these straightforward pyrazole-3-propanoic acid derivatives may possess potential in the design of more potent compounds for intervention with inflammatory and allergic diseases.

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Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Zileuton	Arachidonate 5-lipoxygenase	IC 50 (nM)	800	N/A	N/A	Details