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Acute Lung Injury (ALI) can be caused by various diseases or conditions such as sepsis, pneumonia, trauma, shock, and inhalation of toxic gases. Many efforts have been made to identify new agents capable of treating ALI, and many compounds have shown interesting activities in the treatment of ALI. However, most of these compounds have only been tested for their clinical significance using in vitro and in vivo animal models. In this review, the developments in the design and structural modification of effective active agents for the treatment of ALI is summarized. Firstly, the application of α, β-unsaturated carbonyl moieties as an importantly superior framework in the development of natural product-derived anti -ALI agents is described. As well, the biological activities of the hybrid derivatives from natural products are discussed. Secondly, the potential of synthetic small molecule active compounds in the treatment of ALI is demonstrated. In addition, the structure activity relationship (SAR) and possible mechanisms of action in new chemical molecular entities were investigated. This present mini-review will be useful to scientists in research fields of medicinal chemistry, organic synthesis, and also various biological applications particularly for the development of novel anti -ALI agents. Image 1 • Applications of curcumin and cinnamamide derivatives in anti -ALI drug discovery. • α, β-Unsaturated ketone moiety as an importantly superior skeleton. • Improved anti -ALI activities of molecular hybridization. • Detailed explanation of structure-activity relationships. • Pro-inflammatory cytokines and targeted proteases as effective evaluation strategies. [ABSTRACT FROM AUTHOR]

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), a clinically high mortality disease, has not been effectively treated till now, and the development of anti-acute lung injury drugs is imminent. Acute lung injury was efficiently treated by inhibiting the cascade of inflammation, and reducing the inflammatory response in the lung. A series of novel compounds with highly efficient inhibiting the expression of inflammatory factors were designed by using 4-indolyl-2-aminopyrimidine as the core skeleton. Totally eleven 4-indolyl-2-arylaminopyrimidine derivatives were designed and synthesized. As well, the related anti -ALI activity of these compounds was evaluated. Compounds 6c and 6h showed a superior activity among these compounds, and the inhibition rate of IL-6 and IL-8 release ranged from 62% to 77%, and from 65% to 72%, respectively. Furthermore, most of compounds had no significant cytotoxicity in vitro. The infiltration of inflammatory cells into lung tissue significantly reduced by using compound 6h (20 mg/kg) in the ALI mice model, which achieved the effect of protecting lung tissue and improving ALI. In addition, the inflammatory response was inhibited by using compound 6h through inhibiting phosphorylation of p-38 and ERK in MAPK signaling pathway, and resulted in protective effect on ALI. These data indicated that compound 6h showed good anti-inflammatory activity in vitro and in vivo , which was expected to become a leading compound for the treatment of ALI. [Display omitted] • A novel series of 2-arylamino-4-indolyl pyrimidine derivatives were designed. • Eleven compounds were prepared and evaluated. • Most of the compounds effectively suppressed LPS-induced IL-6 and IL-8. • Compound 6h could be a potent anti-inflammatory candidate for ALI therapy. [ABSTRACT FROM AUTHOR]

Functionalized diazo hydroxylamines are prepared by an efficient Mukaiyama-Mannich addition of α-diazo silyl enolate with nitrones under mild reaction conditions. This protocol provides a variety of 1,2-addition adducts in good to excellent yields, which are potentially of great importance in medicinal chemistry. MgI 2 etherate (MgI 2 ·(OEt 2) n) is the preferred catalyst and this addition proceeds without decomposition of the diazo moiety. Furthermore, this MgI 2 ·(OEt 2) n catalyzed reaction shows unique chemoselectivity towards nitrones with aldehydes or aldimines. Image 1 • MgI 2 etherate could catalyze Mukaiyama-Mannich condensation of α-diazo silyl enolate with nitrones. • This magnesium-catalyzed Mukaiyama-Mannich reaction is mild, efficient and highly chemoselective. • The unique reactivity of this catalytic system was demonstrated. • The condensation of various aromatic or aliphatic nitrones is performed in good to excellent yields. [ABSTRACT FROM AUTHOR]