Article
Journal of Medicinal Chemistry, 2010, Vol. 53, No. 14 5177
benzalkonium chloride treated ears. Left ears received vehicle
only and served as controls. Ear swelling was measured over
three consecutive days with a venire calliper and compared to
the contra lateral control ear. Values represent means of five
BALB/c mice per group.
In a second independent experiment, the anti-inflammtory
effect of 36 in the acute irritant contact dermatitis model at a
dose of 0.1 mg/ear was compared with the effect of the potent
glucocorticoid clobetasol-17-propionate (Karison Crinale Solution,
0.5 mg/g, Dermapharm, Germany) at a dose of 0.005 mg/ear. The
experiment was performed as described above with three groups of
mice treated at different days, each group consisting of five mice
(animal experiments were approved by the state review board
phospholipase A2. Part 2: synthesis of potent and crystallized
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Behnke, M. L.; Hu, B.; Sum, F. W.; Tam, S.; Hu, Y.; Chen, L.;
Kirincich, S. J.; Michalak, R.; Thomason, J.; Ipek, M.; Wu, K.;
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Albert, L.;Xu, X.;Donahue,F.;Ku, M.S.;Keith,J.;Nickerson-Nutter,
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cytosolic phospholipase A2R inhibitors: discovery and in vitro and in
vivo characterization of 4-{3-[5-chloro-2-(2-{[(3,4-dichlorobenzyl)-
sulfonyl]amino}ethyl)-1-(diphenylmethyl)-1H-indol-3-yl]propyl}benzoic
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€
(Munster, G24/96)).
Acknowledgment. This work was supported in part by the
German Research Foundation;DFG, Sonderforschungsber-
eich SFB 656 “Molecular Cardiovascular Imaging”, projects
C6 & Z2.
Supporting Information Available: Purification procedure,
melting points, 1H NMR and MS data of target compounds 8, 9,
11-15, 17-24, and 26-35; assay for iPLA2 and sPLA2 inhibi-
tion; HRMS-HPLC spectra of 36 and 37 and their glucuronides
in the bile of mice treated with 36. This material is available free
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Walters, I.; Wells, E.; Withnall, W. J. Design and synthesis of a
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(21) Yamamoto, M.; Haruna, T.; Imura, K.; Hikita, I.; Furue, Y.;
Higashino, K.; Gahara, Y.; Deguchi, M.; Yasui, K.; Arimura, A.
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A2R inhibitor RSC-3388 on skin inflammation in mice. Pharma-
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