title: Pyrazol-3-propanoic acid derivatives as novel inhibitors of leukotriene biosynthesis in human neutrophils.
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 μM. 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 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.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330 Etiler, Ankara, Turkey.
authors.forename: Burcu
authors.initials: B
authors.lastname: Calışkan
authors.forename: Susann
authors.initials: S
authors.lastname: Luderer
authors.forename: Yağmur
authors.initials: Y
authors.lastname: Özkan
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
authors.forename: Erden
authors.initials: E
authors.lastname: Banoglu
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D015289:Leukotrienes / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011422:Propionates / Q000737:chemistry* / Q000494:pharmacology*; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D011422:Propionates; D011720:Pyrazoles; D001094:Arachidonate 5-Lipoxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C029658:propionic acid