107228-87-5Relevant academic research and scientific papers
Identification of highly potent N-acylethanolamine acid amidase (NAAA) inhibitors: Optimization of the terminal phenyl moiety of oxazolidone derivatives
Li, Yuhang,Chen, Qi,Yang, Longhe,Li, Yanting,Zhang, Yang,Qiu, Yan,Ren, Jie,Lu, Canzhong
, p. 214 - 221 (2017/08/16)
N-acylethanolamine acid amidase (NAAA) is a cysteine hydrolase that participates in the deactivation of fatty acid ethanolamides, such as palmitoylethanolamide (PEA). NAAA inhibition may provide a potential therapeutic strategy for the treatment of diseases in which higher PEA level is desired. In the present study, we reported the structure-activity relationship (SAR) studies for oxazolidone derivatives as NAAA inhibitors. A series of substituents or alkyl replacements for the terminal phenyl ring of oxazolidone derivatives were examined. The results showed that the inhibition potency of these oxazolidone derivatives towards NAAA depends on the sizes, flexibility, and lipophilicity of the terminal groups. SAR results suggested that small lipophilic 3-phenyl substituents or hydroxy-containing 4-phenyl substituents were preferable for optimal potency. Furthermore, the distal aliphatic replacement is also preferred for high inhibitory potency. Rapid dilution and kinetic analysis suggested that oxazolidone derivatives with different terminal phenyl moieties inhibited NAAA via different mechanisms. This study identified several highly potent NAAA inhibitors, including 1a (F215, IC50 = 0.009 μM), 1o (IC50 = 0.061 μM) and 2e (IC50 = 0.092 μM), and also determined structural requirements of oxazolidone derivatives for potent inhibition against NAAA.
Benzophenone Dicarboxylic Acid Antagonists of Leukotriene B4. 2. Structure-Activity Relationships of the Lipophilic Side Chain
Gapinski, D. Mark,Mallett, Barbara E.,Froelich, Larry L.,Jackson, William T.
, p. 2807 - 2813 (2007/10/02)
A series of lipophilic benzophenone dicarboxylic acid derivatives were found to inhibit the binding of the potent chemotoxin leukotriene B4 (LTB4) to its receptor on intact human neutrophils.Activity at the LTB4 receptor was determined by using a 3H>LTB4-binding assay.The structure-activity relationship for the lipophilic side chain was systematically investigated.Compounds with n-alkyl side chains of varying lengths were prepared and tested.Best inhibition of 3H>LTB4 binding was observed with the n-decyl derivative.Analogues with alkyl chains terminated with an aromatic ring showed improved activity.The 6-phenylhexyl side chain was optimal.Substitution on the terminal aromatic ring was also evaluated.Methoxyl, methylsulfinyl, and methyl substituents greatly enhanced the activity of the compound.For a given substituent, the para isomer had the best activity.Thus the nature of the lipophilic side chain can greatly influence the ability of the compounds to inhibit the binding of LTB4 to its receptor on intact human neutrophils.The most active compound from this series, 84 (LY223982), bound to the LTB4 receptor with the affinity approaching that of the agonist.
Dibenz[b,e]oxepinalkanoic acids as nonsteroidal antiinflammatory agents. 3. ω (6,11 Dihydro 11 oxodibenz[b,e]oxepin 2 yl)alkanoic acids
Aultz,McFadden,Lassman
, p. 1499 - 1501 (2007/10/13)
ω-(6,11-Dihydro-11-oxodibenz[b,e]oxepin-2-yl)butyric,-hexanoic, and -octanoic acids were evaluated in the carrageenan paw edema assay. The most active compound, the butyric acid analogue, was 1.80 times more potent than the hexanoic compound, 1.15 times m
