Add time:07/14/2019         Source:sciencedirect.com

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 IC50 values in the range of 1.6–3.5 μM. Moreover, compounds 32, 35, 42, 43 and 44 showed a substantial inhibition of platelet COX-1 activity with IC50 of 2.5, 0.041, 0.3, 0.9 and 0.014 μM, 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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