II-V Compounds

Connolly, T. F.

doi:10.1007/978-1-4684-6201-2_7

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“…39 As outlined in the Introduction, some such heterocyclic derivatives have been claimed as agents for the treatment of inflammatory diseases, however, without providing any in vivo data. 26 Inhibitors containing an α-methyl-2ketothiazole as a metabolically stable serine trap have been presented. 27 The synthesis of thiazole derivatives 13a,b and 18a−c is presented in Schemes 1 and 2.…”

Section: ■ Results and Discusionmentioning

confidence: 99%

“…25 Moreover, heterocyclic derivatives have been claimed as GIVA cPLA 2 inhibitors. 26 Recently, inhibitors containing an α-methyl-2-ketothiazole as a metabolically stable serine trap have been developed, for example, compound 6 (Figure 1). 27 During the past decade, we have designed, synthesized, and studied novel inhibitors targeting various PLA 2 groups.…”

Section: ■ Introductionmentioning

confidence: 99%

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Inhibition of Group IVA Cytosolic Phospholipase A₂ by Thiazolyl Ketones in Vitro, ex Vivo, and in Vivo

et al. 2014

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Group IVA cytosolic phospholipase A2 (GIVA cPLA2) is the rate-limiting provider of pro-inflammatory mediators in many tissues and is thus an attractive target for the development of novel anti-inflammatory agents. In this work, we present the synthesis of new thiazolyl ketones and the study of their activities in vitro, in cells, and in vivo. Within this series of compounds, methyl 2-(2-(4-octylphenoxy)acetyl)thiazole-4-carboxylate (GK470) was found to be the most potent inhibitor of GIVA cPLA2, exhibiting an XI(50) value of 0.011 mole fraction in a mixed micelle assay and an IC50 of 300 nM in a vesicle assay. In a cellular assay using SW982 fibroblast-like synoviocytes, it suppressed the release of arachidonic acid with an IC50 value of 0.6 μM. In a prophylactic collagen-induced arthritis model, it exhibited an anti-inflammatory effect comparable to the reference drug methotrexate, whereas in a therapeutic model, it showed results comparable to those of the reference drug Enbrel. In both models, it significantly reduced plasma PGE2 levels.

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Section: ■ Results and Discusionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Inhibition of Group IVA Cytosolic Phospholipase A₂ by Thiazolyl Ketones in Vitro, ex Vivo, and in Vivo

et al. 2014

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II-V Compounds

Cited by 1 publication

References 50 publications

Inhibition of Group IVA Cytosolic Phospholipase A₂ by Thiazolyl Ketones in Vitro, ex Vivo, and in Vivo

Inhibition of Group IVA Cytosolic Phospholipase A₂ by Thiazolyl Ketones in Vitro, ex Vivo, and in Vivo

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II-V Compounds

Cited by 1 publication

References 50 publications

Inhibition of Group IVA Cytosolic Phospholipase A2 by Thiazolyl Ketones in Vitro, ex Vivo, and in Vivo

Inhibition of Group IVA Cytosolic Phospholipase A2 by Thiazolyl Ketones in Vitro, ex Vivo, and in Vivo

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Inhibition of Group IVA Cytosolic Phospholipase A₂ by Thiazolyl Ketones in Vitro, ex Vivo, and in Vivo

Inhibition of Group IVA Cytosolic Phospholipase A₂ by Thiazolyl Ketones in Vitro, ex Vivo, and in Vivo