Reference of 2-(4-(tert-Butoxycarbonyl)piperazin-1-yl)acetic acid. Aromatic compounds can be divided into two categories: single heterocycles and fused heterocycles. Compound: 2-(4-(tert-Butoxycarbonyl)piperazin-1-yl)acetic acid, is researched, Molecular C11H20N2O4, CAS is 156478-71-6, about Synthesis and Pharmacological Evaluation of Tetrahydro-γ-carboline Derivatives as Potent Anti-inflammatory Agents Targeting Cyclic GMP-AMP Synthase. Author is Tan, Jing; Wu, Bing; Chen, Tingting; Fan, Chen; Zhao, Jiannan; Xiong, Chaodong; Feng, Chunlan; Xiao, Ruoxuan; Ding, Chunyong; Tang, Wei; Zhang, Ao.
The activation of cyclic GMP-AMP synthase (cGAS) by double-stranded DNA is implicated in the pathogenesis of many hyper inflammatory and autoimmune diseases, and the cGAS-targeting small mol. has emerged as a novel therapeutic strategy for treating these diseases. However, the currently reported cGAS inhibitors are far beyond maturity, barely demonstrating in vivo efficacy. Inspired by the structural novelty of compound I (G140), a structural optimization on both its side chain and the central tricyclic core, leads to several subseries of compounds, including those unexpectedly cyclized complex ones. Compound II (R = aminomethyl) bearing an N-glycylglycinoyl side chain was identified as the most potent one with cellular IC50 values of 1.38 and 11.4μM for h- and m-cGAS, resp. Mechanistic studies confirmed its direct targeting of cGAS. Further, compound II (R = aminomethyl) showed superior in vivo anti-inflammatory effects in the lipopolysaccharide-induced mouse model. The encouraging result of compound II (R = aminomethyl) provides solid evidence for further pursuit of cGAS-targeting inhibitors as a new anti-inflammatory treatment.
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Isoquinoline – Wikipedia,
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