Polysubstituted Pyrimidines as mPGES-1 Inhibitors: Discovery of Potent Inhibitors of PGE2 Production with Strong Anti-inflammatory Effects in Carrageenan-Induced Rat Paw Edema was written by Kalcic, Filip;Kolman, Viktor;Ajani, Haresh;Zidek, Zdenek;Janeba, Zlatko. And the article was included in ChemMedChem in 2020.Formula: C14H15BO4 This article mentions the following:
We report an extensive structure-activity relationship optimization of polysubstituted pyrimidines that led to the discovery of 5-butyl-4-(4-benzyloxyphenyl)-6-phenylpyrimidin-2-amine, and its difluorinated analog. These compounds are sub-micromolar inhibitors of PGE2 production (IC50 as low as 12 nM). In order to identify the mol. target of anti-inflammatory pyrimidines, we performed extensive studies including enzymic assays, homol. modeling and docking. The difluorinated analog simultaneously inhibits two key enzymes of the arachidonic acid cascade, namely mPGES-1 and COX-2, with mPGES-1 inhibition being the principal mechanism of action. Other pyrimidines studied are potent mPGES-1 inhibitors with no observed inhibition of COX-1/2 enzymes. Moreover, the two most potent compounds proved to be significantly effective in vivo in a model of acute inflammation, suppressing carrageenan-induced rat paw edema by 36 and 46%. The promising results of this study warrant further preclin. evaluation of selected anti-inflammatory candidates. In the experiment, the researchers used many compounds, for example, (4-((4-Methoxybenzyl)oxy)phenyl)boronic acid (cas: 156635-90-4Formula: C14H15BO4).
(4-((4-Methoxybenzyl)oxy)phenyl)boronic acid (cas: 156635-90-4) belongs to ethers. Ether is less polar than esters, alcohols or amines because of the oxygen atom that is unable to participate in hydrogen bonding due to the presence of bulky alkyl groups on both sides of the oxygen atom. Ethers feature bent C–O–C linkages. In dimethyl ether, the bond angle is 111° and C–O distances are 141 pm. The barrier to rotation about the C–O bonds is low. The bonding of oxygen in ethers, alcohols, and water is similar. In the language of valence bond theory, the hybridization at oxygen is sp3.Formula: C14H15BO4
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem