ChemInform Abstract: Pyrrolidine Inhibitors of Human Cytosolic Phospholipase A₂. Part 2. Synthesis of Potent and Crystallized 4‐Triphenylmethylthio Derivative “Pyrrophenone”.

Abstract

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The orphan G protein-coupled receptor GPR55 promotes cancer cell proliferation via ERK

“…Luminograms were obtained with the Amersham Enhanced Chemiluminescence Detection Kit (GE Healthcare, Uppsala, Sweden). GPR55 promotes cancer cell proliferation C Andradas et al generated in HEK293 cells through this pathway, we inhibited cytosolic phospholipase A2 activity with pyrrophenone (Seno et al, 2001). This compound blocked the increase in cell proliferation induced by GPR55 overexpression (Supplementary Figure 3), suggesting that LPI and/or other potential GPR55 endogenous ligands are produced by HEK-GPR55 cells.…”

OX1 Orexin/Hypocretin Receptor Signaling through Arachidonic Acid and Endocannabinoid Release

“…Most importantly, THL, an inhibitor of DAGL, and pyrrophenone, an inhibitor of cPLA 2 ␣ and - (Seno et al, 2001;Ghomashchi et al, 2010) produced complementary inhibition, together reaching full inhibition. THL was selected as the DAGL inhibitor for detailed investigations because of its greater potency, efficacy, and stability and its likely greater selectivity, compared with RHC-80267.…”

“…The most well characterized (e.g., for selectivity) of these are different pyrrolidine inhibitors for cytosolic PLA 2 (cPLA 2 ) ␣ (Seno et al, 2000(Seno et al, , 2001. A commercially available inhibitor of this type, pyrrophenone (Seno et al, 2001), at 1 M produced significant inhibition of the orexin response (Fig.…”

ASB14780, an Orally Active Inhibitor of Group IVA Phospholipase A2, Is a Pharmacotherapeutic Candidate for Nonalcoholic Fatty Liver Disease

“…These findings led us to hypothesize that IVA-PLA 2 inhibitors may be promising candidates for the treatment of NAFLD and NASH. IVA-PLA 2 -specific inhibitors have already been developed by Wyeth Pharmaceuticals, Shionogi Pharmaceuticals, Astra Zeneca, and the Kokotos and Dennis groups, and include indole derivatives (McKew et al, 2003(McKew et al, , 2006(McKew et al, , 2008Lee et al, 2007), pyrrolidinebased compounds (Seno et al, 2000(Seno et al, , 2001Ono et al, 2002;Flamand et al, 2006), propan-2-ones (Connolly et al, 2002;Ludwig et al, 2006;Hess et al, 2007;Fritsche et al, 2008), and 2-oxoamide compounds (Kokotos et al, 2002(Kokotos et al, , 2004Stephens et al, 2006;Six et al, 2007), respectively. Since none of these inhibitors is orally active, the prospect of using an IVA-PLA 2 inhibitor has been limited.…”